Salivary melatonin onset in youth at familial risk for bipolar disorder

Melatonin secretion and polysomnography (PSG) were compared among a group of healthy adolescents who were at high familial risk for bipolar disorder (HR) and a second group at low familial risk (LR). Adolescent participants (n = 12) were a mean age 14 ± 2.3 years and included 8 females and 4 males. Saliva samples were collected under standardized condition light (red light) and following a 200 lux light exposure over two consecutive nights in a sleep laboratory. Red Light Melatonin onset (RLMO) was defined as saliva melatonin level exceeding the mean of the first 3 readings plus 2 standard deviations. Polysomnography was also completed during each night. HR youth, relative to LR, experienced a significantly earlier melatonin onset following 200 lux light exposure. Polysomnography revealed that LR youth, relative to HR, spent significantly more time in combined stages 3 and 4 (deep sleep) following red light exposure. Additionally, regardless of the group status (HR or LR), there was no significant difference in Red Light Melatonin Onset recorded at home or in the laboratory, implying its feasibility and reliability

Exome-wide association study of pancreatic cancer risk

We conducted a case-control exome-wide association study to discover germline variants in coding regions that affect risk for pancreatic cancer, combining data from 5 studies. We analyzed exome and genome sequencing data from 437 patients with pancreatic cancer (cases) and 1922 individuals not known to have cancer (controls). In the primary analysis, BRCA2 had the strongest enrichment for rare inactivating variants (17/437 cases vs 3/1922 controls) (P=3.27x10(-6); exome-wide statistical significance threshold P<2.5x10(-6)). Cases had more rare inactivating variants in DNA repair genes than controls, even after excluding 13 genes known to predispose to pancreatic cancer (adjusted odds ratio, 1.35, P=.045). At the suggestive threshold (P<.001), 6 genes were enriched for rare damaging variants (UHMK1, AP1G2, DNTA, CHST6, FGFR3, and EPHA1) and 7 genes had associations with pancreatic cancer risk, based on the sequence-kernel association test. We confirmed variants in BRCA2 as the most common high-penetrant genetic factor associated with pancreatic cancer and we also identified candidate pancreatic cancer genes. Large collaborations and novel approaches are needed to overcome the genetic heterogeneity of pancreatic cancer predisposition

Patterns and predictors of family environment among adolescents at high and low risk for familial bipolar disorder

Children's perceptions are important to understanding family environment in the bipolar disorder (BD) high-risk context. Our objectives were to empirically derive patterns of offspring-perceived family environment, and to test the association of family environment with maternal or paternal BD accounting for offspring BD and demographic characteristics. Participants aged 12–21 years (266 offspring of a parent with BD, 175 offspring of a parent with no psychiatric history) were recruited in the US and Australia. We modeled family environment using latent profile analysis based on offspring reports on the Conflict Behavior Questionnaire, Family Adaptability and Cohesion Evaluation Scales, and Home Environment Interview for Children. Parent diagnoses were based on the Diagnostic Interview for Genetic Studies and offspring diagnoses were based on the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Latent class regression was used to test associations of diagnosis and family environment. Two-thirds of all offspring perceived well-functioning family environment, characterized by nurturance, flexibility, and low conflict. Two ‘conflict classes’ perceived family environments low in flexibility and cohesion, with substantial separation based on high conflict with the father (High Paternal Conflict), or very high conflict and rigidity and low warmth with the mother (High Maternal Conflict). Maternal BD was associated with offspring perceiving High Maternal Conflict (OR 2.8, p = 0.025). Clinical care and psychosocial supports for mothers with BD should address family functioning, with attention to offspring perceptions of their wellbeing. More research is needed on the effect of paternal BD on offspring and family dynamics

Substance Use Disorders in Adolescent and Young Adult Relatives of Probands with Bipolar Disorder: What Drives the Increased Risk?

Background Adults with bipolar disorder (BD) have higher rates of substance use disorders (SUDs) compared to the general population. SUD rates in young offspring/relatives of BD probands, as well as factors which drive those rates, are not as well-characterized. Methods We aimed to examine SUD prevalence among adolescent/young adult offspring and relatives of probands with and without BD. Data were collected from five sites in the US and Australia during 2006–2011. Youth offspring/relatives (“Relatives of BD probands;” n = 267; mean age = 16.8 years; ± 2.9 S.D.), identified through a proband family member with DSM-IV BD (Type I or II), were compared to offspring/relatives of control probands (“relatives of control probands;” n = 149; mean age = 17.4 years; ± 2.9 S.D.). Logistic regression with generalized estimating equations was used to compare the groups across a range of substance use and SUD variables. Odds ratios were calculated for lifetime prevalence of substance outcomes. Results Bivariate analyses showed DSM-IV SUDs were more prevalent among relatives of BD probands than among relatives of control probands (29% vs. 18%; p = 0.01). Generalized estimating equation models showed BD mood and childhood-onset externalizing disorders in adolescent and young adult relatives to each significantly increase the odds (OR = 2.80–3.17; p < 0.02) for the development of several substance variables among all relatives, whereas the risk of SUDs in relatives was not increased when the relatives had no mood or externalizing disorders themselves. Conclusion Relatives of BD probands with lifetime mood and externalizing disorders report more substance use/SUDs than relatives of control probands. In contrast, SUD outcomes in relatives of BD probands without mood or externalizing disorders were no different from control relatives without psychopathology. Early recognition and treatment of psychiatric disorders may lead to less substance use in this highly vulnerable population

Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study

To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003-2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission.Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, TREATMENT: 2004-2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts.MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment.This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general

Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk for Suicide Attempts

Objective Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). Method Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. Results After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). Conclusion BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability

Root-Knot Nematodes Exhibit Strain-Specific Clumping Behavior That Is Inherited as a Simple Genetic Trait

Root-knot nematodes are obligate parasites of a wide range of plant species and can feed only on the cytoplasm of living plant cells. In the absence of a suitable plant host, infective juveniles of strain VW9 of the Northern root-knot nematode, Meloidogyne hapla, when dispersed in Pluronic F-127 gel, aggregate into tight, spherical clumps containing thousands of worms. Aggregation or clumping behavior has been observed in diverse genera in the phylum Nematoda spanning free-living species such as Caenorhabditis elegans as well as both plant and animal parasites. Clumping behavior differs between strains of M. hapla and occurs with other species within this genus where strain-specific differences in clumping ability are also apparent. Exposure of M. hapla juveniles to a gradient formed using low levels of cyanide promotes formation of clumps at a preferred cyanide level. Analysis of F2 lines from a cross of M. hapla strains that differ in clump-forming behavior reveals that the behavior segregates as a single, major locus that can be positioned on the genetic map of this nematode. Clumping behavior may be a survival strategy whose importance and function depend on the niche of the nematode strain or species

Maternal Psychosocial Stress during Pregnancy and Placenta Weight: Evidence from a National Cohort Study

To study in a large-scale cohort with prospective data the associations between psychosocial stress during pregnancy and placenta weight at birth. Animal data suggest that the placenta is involved in stress-related fetal programming.; We defined a priori two types of psychosocial stress during pregnancy, life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). We estimated the associations of maternal stress during pregnancy with placenta weight at birth, controlled for length of gestation, by predicting gestational age- and sex-specific z-scores of placenta weight through multiple regression analysis, adjusted for potential confounders (N?=?78,017 singleton pregnancies). Life stress (per increase in stress score by 1, range: 0-18) during pregnancy was associated with increased placenta weight at birth (z-score, reported in 10(-3); B, 14.33; CI, 10.12-18.54). In contrast, emotional symptoms during pregnancy were not associated with placenta weight at birth.; Maternal life stress but not emotional symptoms during pregnancy was associated with increased placenta weight at birth; yet, the association-estimate was rather small. Our results may contribute to a better understanding of the role of the placenta in the regulation of intrauterine processes in response to maternal stress

The impact of nonlinear exposure-risk relationships on seasonal time-series data: modelling Danish neonatal birth anthropometric data

Background Birth weight and length have seasonal fluctuations. Previous analyses of birth weight by latitude effects identified seemingly contradictory results, showing both 6 and 12 monthly periodicities in weight. The aims of this paper are twofold: (a) to explore seasonal patterns in a large, Danish Medical Birth Register, and (b) to explore models based on seasonal exposures and a non-linear exposure-risk relationship. Methods Birth weight and birth lengths on over 1.5 million Danish singleton, live births were examined for seasonality. We modelled seasonal patterns based on linear, U- and J-shaped exposure-risk relationships. We then added an extra layer of complexity by modelling weighted population-based exposure patterns. Results The Danish data showed clear seasonal fluctuations for both birth weight and birth length. A bimodal model best fits the data, however the amplitude of the 6 and 12 month peaks changed over time. In the modelling exercises, U- and J-shaped exposure-risk relationships generate time series with both 6 and 12 month periodicities. Changing the weightings of the population exposure risks result in unexpected properties. A J-shaped exposure-risk relationship with a diminishing population exposure over time fitted the observed seasonal pattern in the Danish birth weight data. Conclusion In keeping with many other studies, Danish birth anthropometric data show complex and shifting seasonal patterns. We speculate that annual periodicities with non-linear exposure-risk models may underlie these findings. Understanding the nature of seasonal fluctuations can help generate candidate exposures