Investigation in the relationship between childhood adversity and cognitive function in psychosis and individuals at clinical high risk of psychosis

Background An increasing body of research is suggesting that childhood trauma and adversity may be associated with various adverse mental health outcomes, including psychosis. Cognitive functioning is often compromised in psychosis, and research has shown that there may be a link between early trauma and cognitive impairment in people with psychosis. No systematic review of the literature of this link has been undertaken, and very few studies have examined samples of individuals at high clinical risk for psychosis, to assess whether the potential link between adversity and cognitive functioning exists, without the confounding factors of length of illness, antipsychotic medication and chronicity of symptoms. Method The systematic review of all relevant electronic databases investigates the research to date on the association between childhood adverse experiences and cognitive ability in psychosis, and the conclusions that can be drawn from the existing literature, taking into account relevant considerations regarding sample, methodology and statistical analysis. The subsequent empirical study utilizes a sample at clinical high risk of developing psychosis, and a healthy control group to investigate whether any putative association in specific domains of cognitive functioning, or global cognitive ability and childhood adversity exist in those at clinical high risk, compared to controls. Results The systematic review indicated that at present, the literature looking into childhood adversity and cognitive ability in relation to psychosis is heterogeneous, with some studies finding that this association only occurs in patients, whilst others suggest it only occurs in the control groups. Some studies found it to be specific to certain cognitive domains, whilst others suggest it was a more global impairment. Methodology, samples and analysis differed considerably across studies, and likely contribute to the heterogeneity of the literature. The empirical paper showed a significant interaction effect between group (high risk versus controls) in the high childhood adversity group, in relation to global cognitive ability. Interestingly, this was not related to psychotic symptom severity or distress. Conclusion Several limitations of the existing studies limit the conclusions that can be drawn from the existing evidence regarding the link between childhood adversity and cognitive ability, and future research in prodromal samples is essential. The empirical study showed that there is a link between childhood adversity and cognitive ability in those at clinical high risk of developing psychosis, before disorder onset, that is not present in controls. This suggests that this may form a vulnerability in those at high risk for psychosis, rather than a more general mechanism present in the typical population

Sexual and relationship intimacy among women with provoked vestibulodynia and their partners : associations with sexual satisfaction, sexual function, and pain self-efficacy

Introduction Provoked vestibulodynia (PVD) is the most frequent subtype of vulvodynia. Women report negative consequences of PVD on their sexual and romantic relationships. Researchers have recently highlighted the importance of examining interpersonal factors such as intimacy, and of including both women and their partners in study designs. Aim The aim of this study was to investigate sexual and relationship intimacy as defined by the Interpersonal Process Model of Intimacy and their associations with sexual satisfaction, sexual function, pain self-efficacy, and pain intensity among women with PVD and their partners. Methods Ninety-one heterosexual women (M age = 27.38, SD = 6.04) diagnosed with PVD and their partners (M age = 29.37, SD = 7.79) completed measures of sexual and relationship intimacy, sexual satisfaction, sexual function, pain self-efficacy, and pain intensity. Main Outcome Measures Dependent measures were the (i) Global Measure of Sexual Satisfaction Scale; (ii) Female Sexual Function Index; (iii) Painful Intercourse Self-Efficacy Scale; and (iv) visual analog scale of pain intensity during intercourse. Results After controlling for women's age, women's greater sexual intimacy (β = 0.49, P < 0.001) was associated with women's greater sexual satisfaction and higher pain self-efficacy (β = 0.39, P = 0.001), beyond the effects of partners’ sexual intimacy. Also, women's greater sexual intimacy (β = 0.24, P = 0.05) and women's greater relationship intimacy (β = 0.54, P = 0.003) were associated with greater women's sexual function, beyond the effects of partners’ sexual and relationship intimacy. Conclusions Women's self-reported sexual and relationship intimacy in the couple relationship may promote higher sexual satisfaction, sexual function, and pain self-efficacy, as well as possibly foster greater sexual well-being among women with PVD. The authors discuss implications for the inclusion of emotional and interpersonal aspects of the couple's dynamic in clinical interventions and future research in PVD

O6-8 Rethinking schools as a setting for physical activity promotion in the 21st Century - A position paper from the Erasmus+ 2PASS 4Health project

Background Schools are ideally placed to provide children and adolescents with multiple opportunities to be or learn to be physically active. However, key reviews have reported that interventions to date have largely failed to have any long-term impact on overall physical activity levels. In this position paper, greater attention to key issues is needed to realise the full potential of schools and ideal physical activity for health promotion setting. Methods This study draws on multi-author expertise to develop a position paper to advance opinion on school-based programmes. Collaborative conceptual thinking was established through various tools such as literature review, evidence synthesis and online and in person meetings. Results/Discussion The adoption of a systems approach is valuable for understanding the complexities of the school setting and to support the implementation of whole-of-school initiatives. Furthermore, we contend that the full range of physical, cognitive, emotional and social benefits that physical activity provides should be considered, rather than a narrow focus solely on physical activity levels. Interdisciplinary research questions are most useful in exploring and evaluating whole-of-school approaches. Informed by process, impact and outcome evaluation and implementation science, both qualitative and quantitative research methodologies and a move beyond traditional research design are needed to advance our knowledge of what works, for whom and in what context. Case studies from several European countries will be presented to illustrate examples of systems approaches in action. This includes examples at multiple levels firstly, a national approach including a Physical Education curriculum reformation (Portugal), a regional approach such as a county council partnership with a University to support physical activity promotion (France) and a local approach at the school level i.e. a whole-of-school physical activity programme (Spain and Ireland). Conclusion From authors expertise and reflection, this paper makes recommendations on the nature of the evidence required to bridge the implementation gap, sustain and scale-up innovative approaches to whole-of-school programmes

Thermokarst processes increase the supply of stabilizing surfaces and elements (Fe, Mn, Al, and Ca) for mineral–organic carbon interactions

The stabilizing properties of mineral–organic carbon (OC) interactions have been studied in many soil environments (temperate soils, podzol lateritic soils, and paddy soils). Recently, interest in their role in permafrost regions is increasing as permafrost was identified as a hotspot of change. In thawing ice-rich permafrost regions, such as the Yedoma domain, 327–466 Gt of frozen OC is buried in deep sediments. Interactions between minerals and OC are important because OC is located very near the mineral matrix. Mineral surfaces and elements could mitigate recent and future greenhouse gas emissions through physical and/or physicochemical protection of OC. The dynamic changes in redox and pH conditions associated with thermokarst lake formation and drainage trigger metal-oxide dissolution and precipitation, likely influencing OC stabilization and microbial mineralization. However, the influence of thermokarst processes on mineral–OC interactions remains poorly constrained. In this study, we aim to characterize Fe, Mn, Al, and Ca minerals and their potential protective role for OC. Total and selective extractions were used to assess the crystalline and amorphous oxides or complexed metal pools as well as the organic acids found within these pools. We analyzed four sediment cores from an ice-rich permafrost area in Central Yakutia, which were drilled (i) in undisturbed Yedoma uplands, (ii) beneath a recent lake formed within Yedoma deposits, (iii) in a drained thermokarst lake basin, and (iv) beneath a mature thermokarst lake from the early Holocene period. We find a decrease in the amount of reactive Fe, Mn, Al, and Ca in the deposits on lake formation (promoting reduction reactions), and this was largely balanced by an increase in the amount of reactive metals in the deposits on lake drainage (promoting oxidation reactions). We demonstrate an increase in the metal to C molar ratio on thermokarst process, which may indicate an increase in metal–C bindings and could provide a higher protective role against microbial mineralization of organic matter. Finally, we find that an increase in mineral–OC interactions corresponded to a decrease in CO2 and CH4 gas emissions on thermokarst process

ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas

&lt;b&gt;Objective&lt;/b&gt; &lt;i&gt;ABCB1&lt;/i&gt; encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; The best candidates from fine-mapping analysis of 21 &lt;i&gt;ABCB1&lt;/i&gt; SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Result&lt;/b&gt; Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, &lt;i&gt;ABCB1&lt;/i&gt; expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; Our study represents the largest analysis of &lt;i&gt;ABCB1&lt;/i&gt; SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.&lt;p&gt;&lt;/p&gt

Phosphorylation and modulation of hyperpolarization-activated HCN4 channels by protein kinase A in the mouse sinoatrial node

The sympathetic nervous system increases heart rate by activating β adrenergic receptors and increasing cAMP levels in myocytes in the sinoatrial node. The molecular basis for this response is not well understood; however, the cardiac funny current (If) is thought to be among the end effectors for cAMP signaling in sinoatrial myocytes. If is produced by hyperpolarization-activated cyclic nucleotide–sensitive (HCN4) channels, which can be potentiated by direct binding of cAMP to a conserved cyclic nucleotide binding domain in the C terminus of the channels. β adrenergic regulation of If in the sinoatrial node is thought to occur via this direct binding mechanism, independent of phosphorylation. Here, we have investigated whether the cAMP-activated protein kinase (PKA) can also regulate sinoatrial HCN4 channels. We found that inhibition of PKA significantly reduced the ability of β adrenergic agonists to shift the voltage dependence of If in isolated sinoatrial myocytes from mice. PKA also shifted the voltage dependence of activation to more positive potentials for heterologously expressed HCN4 channels. In vitro phosphorylation assays and mass spectrometry revealed that PKA can directly phosphorylate at least 13 sites on HCN4, including at least three residues in the N terminus and at least 10 in the C terminus. Functional analysis of truncated and alanine-substituted HCN4 channels identified a PKA regulatory site in the distal C terminus of HCN4, which is required for PKA modulation of If. Collectively, these data show that native and expressed HCN4 channels can be regulated by PKA, and raise the possibility that this mechanism could contribute to sympathetic regulation of heart rate

The cortical thickness phenotype of individuals with <i>DISC1</i> translocation resembles schizophrenia

BACKGROUND. The disrupted in schizophrenia 1 (DISC1) gene locus was originally identified in a Scottish pedigree with a high incidence of psychiatric disorders that is associated with a balanced t(1;11)(q42.1;q14.3) chromosomal translocation. Here, we investigated whether members of this family carrying the t(1;11)(q42.1;q14.3) translocation have a common brain-related phenotype and whether this phenotype is similar to that observed in schizophrenia (SCZ), using multivariate pattern recognition techniques. METHODS. We measured cortical thickness, cortical surface area, subcortical volumes, and regional cerebral blood flow (rCBF) in healthy controls (HC) (n = 24), patients diagnosed with SCZ (n = 24), patients diagnosed with bipolar disorder (BP) (n = 19), and members of the original Scottish family (n = 30) who were either carriers (T+) or noncarriers (T–) of the DISC1 translocation. Binary classification models were developed to assess the differences and similarities across groups. RESULTS. Based on cortical thickness, 72% of the T– group were assigned to the HC group, 83% of the T+ group were assigned to the SCZ group, and 45% of the BP group were classified as belonging to the SCZ group, suggesting high specificity of this measurement in predicting brain-related phenotypes. Shared brain-related phenotypes between SCZ and T+ individuals were found for cortical thickness only. Finally, a classification accuracy of 73% was achieved when directly comparing the pattern of cortical thickness of T+ and T– individuals. CONCLUSION. Together, the results of this study suggest that the DISC1 translocation may increase the risk of psychiatric disorders in this pedigree by affecting neurostructural phenotypes such as cortical thickness. FUNDING. This work was supported by the National Health Service Research Scotland, the Scottish Translational Medicine Research Collaboration, the Innovative Medicines Initiative (IMI), the Engineering and Physical Sciences Research Council (EPSRC), The Wellcome Trust, the National Institute of Health Research (NIHR), and Pfizer