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A significant proportion of the global burden of disease can be attributed to mental illness. Despite important advances in identifying risk factors for mental health conditions, the biological processing underlying causal pathways to disease onset remain poorly understood. This represents a limitation to implement effective prevention and the development of novel pharmacological treatments. Epigenetic mechanisms have emerged as mediators of environmental and genetic risk factors which might play a role in disease onset, including childhood adversity (CA) and cannabis use (CU). Particularly, human research exploring DNA methylation has provided new and promising insights into the role of biological pathways implicated in the aetio-pathogenesis of psychiatric conditions, including: monoaminergic (Serotonin and Dopamine), GABAergic, glutamatergic, neurogenesis, inflammatory and immune response and oxidative stress. While these epigenetic changes have been often studied as disease-specific, similarly to the investigation of environmental risk factors, they are often transdiagnostic. Therefore, we aim to review the existing literature on DNA methylation from human studies of psychiatric diseases (i) to identify epigenetic modifications mapping onto biological pathways either transdiagnostically or specifically related to psychiatric diseases such as Eating Disorders, Post-traumatic Stress Disorder, Bipolar and Psychotic Disorder, Depression, Autism Spectrum Disorder and Anxiety Disorder, and (ii) to investigate a convergence between some of these epigenetic modifications and the exposure to known risk factors for psychiatric disorders such as CA and CU, as well as to other epigenetic confounders in psychiatry research.
Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD).
Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons.
In case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74).
Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.
A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone.
We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders.
There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88).
Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.
Climbing cacti with edible fruits have been proposed as new dryland fruit crops because their high water-use efficiency reduces water requirement. One lineage of climbers in the cactus family, the Hylocereus group of Selenicereus, includes several species that produce edible fruits and is currently cultivated around the world. Fruits are known as pitahayas, pitayas or dragon fruit. Here, by means of ecological niche-based modelling and analytical hierarchical modelling, the optimal areas for cultivating the three main species of this group in Mesoamerica – Selenicereus costaricensis, Selenicereus ocamponis and Selenicereus undatus – are identified. Data on distribution, physiological requirement and host preferences are taken into account to carry out ecological modelling for current and future scenarios of climate and determine its impact on cultivation. Two MIROC climatic future models, one optimistic (ssp216) and a pessimistic (ssp585) were selected and 554 records from Mexico and Central America were gathered. For all three species, temperature and precipitation seasonality, and solar radiation were the most significant variables in the niche modelling. In addition, for S. undatus the most important hosts, three species of mesquite legume trees were significant to forecast suitable areas for planting. Large areas on the Pacific side from Sinaloa to Costa Rica were predicted as favourable for cultivating the studied three species. Future scenarios of climate change predicted increase of suitable areas for two species and in particular for S. undatus the increment was the largest. Therefore, dragon fruits are corroborated as promising fruits in view of climate change.
This project investigates the participation of rural Galician women in social movements regarding labor and rural concerns from 1970 to 1990, with a comparative and interdisciplinary approach. Based on the studies we have analyzed we can conclude that the recognition of rural women and their roles in their organizations have been consolidated in recent years. Rural women have gradually become significant social players in the development of their communities and, consequently, their economies. This study also demonstrates that participation in organizations plays a major role in the development of women's identities by changing the rural definition of gender. In the case of Galician women, historical relegation is evident as the empowerment of rural women did not begin until a group of feminist women became members of the Executive Board of Sindicato Labrego Galego. The driving force behind this empowerment was the creation of organizations for women with clear and specific objectives.
There has been a recent trend in medical research towards a more collaborative relationship between statisticians and clinical investigators. This has led to an increased focus on the most efficient and effective ways to structure, conduct, and measure the impact of organizations that provide statistical services to clinical investigators. Several recent guidelines and recommendations on the conduct of statistical consulting services(SCSs) have been made in response to this need, focusing on larger SCSs consisting primarily of faculty and staff statisticians. However, the application of these recommendations to consulting services primarily staffed by graduate students, which have the dual role of providing a professional service and training, remains unclear.
Guidelines and recommendations, primarily from the Clinical and Translational Science (CTSA) consortium, were applied to a SCS staffed primarily by graduate students in an academic health center. A description of the organizational structure and outcomes after 3 years of operation is presented.
The guidelines recommended by the CTSA consortium and other groups were successfully incorporated into the graduate consulting laboratory. At almost one new project request per week, the consulting laboratory demonstrated a large bandwidth and had an excellent feedback from investigators.
Guidelines developed for larger statistical consulting organizations are able to be applied in student-led consultation organizations. Outcomes and recommendations from 3.5 years of operation are used to describe the successes and challenges we have encountered.
Various psychological and biological pathways have been proposed as mediators between childhood adversity (CA) and psychosis. A systematic review of the evidence in this domain is needed. Our aim is to systematically review the evidence on psychological and biological mediators between CA and psychosis across the psychosis spectrum. This review followed PRISMA guidelines. Articles published between 1979 and July 2019 were identified through a literature search in OVID (PsychINFO, Medline and Embase) and Cochrane Libraries. The evidence by each analysis and each study is presented by group of mediator categories found. The percentage of total effect mediated was calculated. Forty-eight studies were included, 21 in clinical samples and 27 in the general population (GP) with a total of 82 352 subjects from GP and 3189 from clinical studies. The quality of studies was judged as ‘fair’. Our results showed (i) solid evidence of mediation between CA and psychosis by negative cognitive schemas about the self, the world and others (NS); by dissociation and other post-traumatic stress disorder symptoms; and through an affective pathway in GP but not in subjects with disorder; (iii) lack of studies exploring biological mediators. We found evidence suggesting that various overlapping and not competing pathways involving post-traumatic and mood symptoms, as well as negative cognitions contribute partially to the link between CA and psychosis. Experiences of CA, along with relevant mediators should be routinely assessed in patients with psychosis. Evidence testing efficacy of interventions targeting such mediators through cognitive behavioural approaches and/or pharmacological means is needed in future.
The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.
A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.
The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients.
Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.
Recent studies have led to suggest that the multifunctional protein clusterin could be envisaged as a potential diagnostic biomarker of addictive behaviours. However, this hypothesis has not been yet tested in nicotine addicts.
We have studied possible associations between clusterin levels in saliva from smokers under cessation treatment and variables related to tobacco consumption, dependence and addiction.
Eighty-one patients were included in an ambulatory smoking cessation programme that involved the use of pharmacological and behavioural therapy. The participants underwent psychological assessment of addiction and dependence (DAST-20, ASSIST, Fagerström tests) and provided saliva samples at the onset of the intervention and 6 months after smoking discontinuation to study the evolution of clusterin levels by enzyme-linked immunosorbent assays.
Clusterin concentration did not correlate with nicotine addiction/dependence scores but was significantly elevated in smokers with prolonged tobacco use and high intensity of tobacco consumption. Moreover, the levels of the protein significantly decreased 6 months after smoking cessation.
The results obtained provide strong evidence of a close association between tobacco use and salivary clusterin, a protein that emerges as a biomarker of tobacco toxicity with potential interest to monitor the beneficial effects of smoking cessation.
This study examined (1) the association of dietary energy density from solid (EDS) and solid plus liquids (EDSL) with adiposity and cardiometabolic risk factors (CRF) in children with overweight and obesity, (2) the effect of under-reporting on the mentioned associations and (3) whether the association between ED and body composition and CRF is influenced by levels of physical activity. In a cross-sectional design, 208 overweight and obese children (8–12-year-old; 111 boys) completed two non-consecutive 24 h recalls. ED was calculated using two different approaches: EDS and EDSL. Under-reporters were determined with the Goldberg method. Body composition, anthropometry and fasting blood sample measurements were performed. Moderate to vigorous physical activity (MVPA) was registered with accelerometers (7-d-register). Linear regressions were performed to evaluate the association of ED with the previously mentioned variables. Neither EDS nor EDSL were associated with body composition or CRF. However, when under-reporters were excluded, EDS was positively associated with BMI (P=0·019), body fat percentage (P=0·005), abdominal fat (P=0·008) and fat mass index (P=0·018), while EDSL was positively associated with body fat percentage (P=0·008) and fat mass index (P=0·026). When stratifying the group according to physical activity recommendations, the aforementioned associations were only maintained for non-compliers. Cluster analysis showed that the low-ED and high-MVPA group presented the healthiest profile for all adiposity and CRF. These findings could partly explain inconsistencies in literature, as we found that different ED calculations entail distinct results. Physical activity levels and excluding under-reporters greatly influence the associations between ED and adiposity in children with overweight and obesity.
Jumping to conclusions (JTC), which is the proneness to require less information before forming beliefs or making a decision, has been related to formation and maintenance of delusions. Using data from the National Institute of Health Research Biomedical Research Centre Genetics and Psychosis (GAP) case–control study of first-episode psychosis (FEP), we set out to test whether the presence of JTC would predict poor clinical outcome at 4 years.
One-hundred and twenty-three FEP patients were assessed with the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF) and the probabilistic reasoning ‘Beads’ Task at the time of recruitment. The sample was split into two groups based on the presence of JTC bias. Follow-up data over an average of 4 years were obtained concerning clinical course and outcomes (remission, intervention of police, use of involuntary treatment – the Mental Health Act (MHA) – and inpatient days).
FEP who presented JTC at baseline were more likely during the follow-up period to be detained under the MHA [adjusted OR 15.62, 95% confidence interval (CI) 2.92–83.54, p = 0.001], require intervention by the police (adjusted OR 14.95, 95% CI 2.68–83.34, p = 0.002) and have longer admissions (adjusted IRR = 5.03, 95% CI 1.91–13.24, p = 0.001). These associations were not accounted for by socio-demographic variables, IQ and symptom dimensions.
JTC in FEP is associated with poorer outcome as indicated and defined by more compulsion police intervention and longer periods of admission. Our findings raise the question of whether the implementation of specific interventions to reduce JTC, such as Metacognition Training, may be a useful addition in early psychosis intervention programmes.
The aim of this study was to assess the relationships between class-related anxiety with perceived control, teacher-reported behavioral engagement, behavioral disaffection, and academic performance. Participants were 355 compulsory secondary students (9th and 10th grades; Mean age = 15.2 years; SD = 1.8 years). Structural equation models revealed performance was predicted by perceived control, anxiety, disaffection, and engagement. Perceived control predicted anxiety, disaffection, and engagement. Anxiety predicted disaffection and engagement, and partially mediated the effects from control on disaffection (β = –.277, p < .005; CI = –.378, –.197) and engagement (β = .170, p < .002; CI = .103 .258). The negative association between anxiety and performance was mediated by engagement and disaffection (β = –.295, p < .002; CI = –.439, –.182). Anxiety, engagement, and disaffection mediated the effects of control on performance (β = .352, p < .003; CI = .279, .440). The implications of these results are discussed in the light of current theory and educational interventions.
The franciscana dolphin (Pontoporia blainvillei) is a small coastal dolphin endemic to the south-western Atlantic Ocean. Incidental captures in fishing gillnets is possibly the greatest conservation concern for this species, and occurs within most of its geographical distribution. The aim of this paper is to determine the biological parameters of franciscana dolphin by-caught from artisanal coastal fisheries of the southern Buenos Aires province, Argentina. Between 2003 and 2009, carcasses of 54 incidentally captured franciscanas were collected. The age, sexual and physical maturity and body condition of each specimen was determined. The sex-ratio of the by-caught dolphins did not differ from parity and, consistent with other areas, juveniles younger than 4 yr old were captured in higher proportion (69%). In addition, 74% of the entangled animals were sexually immature and 85% physically immature. Sexually immature dolphins were predominant in the spring, a period which coincides with the breeding season. An assessment of the body condition of captured franciscanas suggests that entanglements were not associated with a disease or physiological disorder. The results presented here are important to assess the impact of artisanal fisheries on the population of franciscana dolphins in the southernmost area of its distribution.
The aim of this study was to determine the prevalence of bullying in its various forms from the perspective of all of the individuals involved (victims, bullies, and witnesses) and to explore its distribution as a function of gender. The study had a correlational design and used a representative sample of 1500 Spanish students attending compulsory secondary education in the academic year 2007–2008. It applied an instrument measuring different types of bullying, taken from the studies conducted by Díaz-Aguado, Martínez, and Martín (2004) and the Defensor del Pueblo (Spanish Ombudsman’s Office)-UNICEF (2007). The findings reveal that all the types of bullying considered take place at school and that there is an inverse relationship between the severity and the prevalence of bullying behaviors, with verbal abuse proving to be the most common type of abusive behavior. Boys are involved in all kinds of bullying incidents as bullies significantly more often than girls are, except in cases involving ‘talking about someone behind their back’; in these situations, girls are involved significantly more often as bullies than boys are. As for victimization, boys are victims of direct physical abuse significantly more often than girls are, while girls are more often the subject of malicious gossip.
A before-after prospective surveillance study to assess the impact of a multidimensional infection control approach for the reduction of catheter-associated urinary tract infection (CAUTI) rates.
Pediatric intensive care units (PICUs) of hospital members of the International Nosocomial Infection Control Consortium (INICC) from 10 cities of the following 6 developing countries: Colombia, El Salvador, India, Mexico, Philippines, and Turkey.
We performed a prospective active surveillance to determine rates of CAUTI among 3,877 patients hospitalized in 10 PICUs for a total of 27,345 bed-days. The study was divided into a baseline period (phase 1) and an intervention period (phase 2). In phase 1, surveillance was performed without the implementation of the multidimensional approach. In phase 2, we implemented a multidimensional infection control approach that included outcome surveillance, process surveillance, feedback on CAUTI rates, feedback on performance, education, and a bundle of preventive measures. The rates of CAUTI obtained in phase 1 were compared with the rates obtained in phase 2, after interventions were implemented.
During the study period, we recorded 8,513 urinary catheter (UC) days, including 1,513 UC-days in phase 1 and 7,000 UC-days in phase 2. In phase 1, the CAUTI rate was 5.9 cases per 1,000 UC-days, and in phase 2, after implementing the multidimensional infection control approach for CAUTI prevention, the rate of CAUTI decreased to 2.6 cases per 1,000 UC-days (relative risk, 0.43 [95% confidence interval, 0.21–1.0]), indicating a rate reduction of 57%.
Our findings demonstrated that implementing a multidimensional infection control approach is associated with a significant reduction in the CAUTI rate of PICUs in developing countries.
The guanaco Lama guanicoe was the only large native herbivore widely distributed across Patagonia until the introduction of domestic sheep Ovis aries. Guanacos have declined because of competition with sheep for forage, high hunting pressure and habitat degradation. Península Valdés is a protected area where sheep ranching is the predominant activity. A ranch formerly dedicated to sheep production was converted into a private wildlife reserve, from which all the sheep were removed in 2005. We studied changes in guanaco abundance inside and outside the reserve after sheep removal, and also plant cover of various vegetation types. We found that guanaco abundance was higher inside than outside the reserve, and increased by three-fold within 3 years. Total plant cover and grass cover were higher inside than outside the reserve. Our results showed that guanacos reacted rapidly to changes in management, and suggest that even at a high density guanacos would not be as damaging to the vegetation as sheep. Although management changes resulted in significant changes in guanaco abundance locally, the size of a protected area influences the persistence of wild populations. A large herbivore such as the guanaco needs to be managed across large areas. We believe it is necessary to implement a management plan for Península Valdés that allows for the coexistence of sustainable livestock production and healthy wildlife populations.
Researchers, governments and conservation organizations recognize that the long-term integrity of protected areas (PAs) in low-income nations depends upon the support of indigenous and rural communities that live within or around them. Thus, understanding the determinants of residents’ attitudes towards PAs might provide guidance in the design, implementation and evaluation of this strategic form of biodiversity conservation. This paper (1) compares urban and rural residents’ perceptions of the impact of a PA and (2) analyses the association between the perception of economic, social and environmental impacts, and overall attitude towards the PA. Information was collected among urban and rural residents living in the vicinity of the Dandeli Wildlife Sanctuary in the Western Ghats (Karnataka, India). Local residents’ attitudes towards the PA were mainly positive, especially among urban residents. Multivariate analysis showed a positive association between the perception of economic benefits and individual attitudes towards the PA. There was no statistically significant association between attitudes towards the PA and perception of social and environmental impacts. Future research should address whether positive attitudes translate into more sustainable behaviours.
The fourth season of the Burials and Identity component of the Desert Migrations Project in 2010 focused on completion of excavation work at two main cemeteries (TAG001 and TAG012) and smaller-scale sampling work at a number of nearby cemeteries. The investigation of a number of burials in a semi-nucleated escarpment cemetery TAG063 produced interesting new information on Proto-Urban Garamantian funerary rites, dating to the latter centuries BC. The excavations at TAG001 were extended to two areas of the cemetery characterised by different burial types to the stepped tombs that were excavated in 2009. A second type of fairly monumental burial was identified, but these had been heavily robbed and it was not possible to demonstrate conclusively that these pre-dated the stepped tombs. Most of the other burials excavated were simple shaft burials and were relatively sparsely furnished with imported goods, in comparison with the larger tombs, though quite a lot of organic material was identified (matting, wood, gourds, textiles and leather). At TAG012, a series of additional mudbrick tombs was emptied. All had been robbed, but pockets of the original fill and associated finds survived intact, yielding some interesting assemblages. The majority of these tombs appear to be Late Garamantian, though some contained artefacts from much earlier times.