A prospective population-based study of gestational vitamin D status and brain morphology in preadolescents

Low vitamin D level during pregnancy has been associated with adverse neurodevelopmental outcomes such as autism spectrum disorders (ASD) in children. However, the underlying neurobiological mechanism remains largely unknown. This study investigated the association between gestational 25-hydroxyvitamin D [25(OH)D] concentration and brain morphology in 2597 children at the age of 10 years in the population-based Generation R Study. We studied both 25(OH)D in maternal venous blood in mid-gestation and in umbilical cord blood at delivery, in relation to brain volumetric measures and surface-based cortical metrics including cortical thickness, surface area, and gyrification using linear regression. We found exposure to higher maternal 25(OH)D concentrations in mid-gestation was associated with a larger cerebellar volume in children (b ​= ​0.02, 95%CI 0.001 to 0.04), however this association did not remain after co

Disease-specific, neurosphere-derived cells as models for brain disorders

There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery

Using job strain and organizational justice models to predict multiple forms of employee performance behaviours among Australian policing personnel

The overall purpose of this investigation was to examine the relationship between stress-related working conditions and three forms of employee performance behaviours: in-role behaviours, citizenship behaviours directed at other individuals and citizenship behaviours directed at the organization. The potentially stressful working conditions were based on the job strain model (incorporating job demands, job control and social support) as well as organizational justice theory. A sample of Australian-based police officers (n = 640) took part in this study and the data were collected via a mail-out survey. Multiple regression analyses were undertaken to assess both the strength and the nature of the relationships between the working conditions and employee performance and these analyses included tests for additive, interactional and curvilinear effects. The overall results indicated that a significant proportion of the explained variance in all three outcome measures was attributed to the additive effects of demand, control and support. The level of variance associated with the organizational justice dimensions was relatively small, although there were signs that specific dimensions of justice may provide unique insights into the relationship between job stressors and employee performance. The implications of these and other notable findings are discussed.<br /

Gestational Vitamin D deficiency and autism-related traits: The Generation R Study

There is intense interest in identifying modifiable risk factors associated with autism-spectrum disorders (ASD). Autism-related traits, which can be assessed in a continuous fashion, share risk factors with ASD, and thus can serve as informative phenotypes in population-based cohort studies. Based on the growing body of research linking gestational Vitamin D deficiency with altered brain development, this common exposure is a candidate modifiable risk factor for ASD and autism-related traits. The association between gestational Vitamin D deficiency and a continuous measure of autism-related traits at ∼6 years (Social Responsiveness Scale; SRS) was determined in a large population-based cohort of mothers and their children (n=4229). 25-hydroxyVitamin D (25OHD) was assessed from maternal mid-gestation sera and from neonatal sera (collected from cord blood). Vitamin D deficiency was defined as 25OHD concentrations less than 25 nmol l-1. Compared with the 25OHD sufficient group (25OHD>50 nmol l-1), those who were 25OHD deficient had significantly higher (more abnormal) SRS scores (mid-gestation n=2866, β=0.06, P<0.001; cord blood n=1712, β=0.03, P=0.01). The findings persisted (a) when we restricted the models to offspring with European ancestry, (b) when we adjusted for sample structure using genetic data, (c) when 25OHD was entered as a continuous measure in the models and (d) when we corrected for the effect of season of blood sampling. Gestational Vitamin D deficiency was associated with autism-related traits in a large population-based sample. Because gestational Vitamin D deficiency is readily preventable with safe, cheap and accessible supplements, this candidate risk factor warrants closer scrutiny

Cohort profile: the Australian genetics of depression study

PURPOSE:Depression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of individuals who have been diagnosed with depression at some point in their lifetime. The purpose of establishing this cohort is to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants. PARTICIPANTS:A total of 20 689 participants were recruited through the Australian Department of Human Services and a media campaign, 75% of whom were female. The average age of participants was 43 years±15 years. Participants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA sample (75%) were sent a saliva kit in the mail. FINDINGS TO DATE:95% of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a lifetime depressive episode. 68% of the sample report having been diagnosed with another psychiatric disorder in addition to depression. In line with findings from clinical trials, only 33% of the sample report responding well to the first antidepressant they were prescribed. FUTURE PLANS:A number of analyses to investigate the genetic architecture of depression and common comorbidities will be conducted. The cohort will contribute to the global effort to identify genetic variants that increase risk to depression. Furthermore, a thorough investigation of genetic and psychosocial predictors of antidepressant response and side effects is planned.Enda M Byrne, Katherine M Kirk, Sarah E Medland, John J McGrath, Lucia Colodro-Conde, Richard Parker ... et al

Epidemiology and Treatment Guidelines of Negative Symptoms in Schizo-phrenia in Central and Eastern Europe: A Literature Review

AIM: To gather and review data describing the epidemiology of schizophrenia and clinical guidelines for schizophrenia therapy in seven Central and Eastern European countries, with a focus on negative symptoms. Methods : A literature search was conducted which included publications from 1995 to 2012 that were indexed in key databases. Results : Reports of mean annual incidence of schizophrenia varied greatly, from 0.04 to 0.58 per 1,000 population. Lifetime prevalence varied from 0.4% to 1.4%. One study reported that at least one negative symptom was present in 57.6% of patients with schizophrenia and in 50-90% of individuals experiencing their first episode of schizophrenia. Primary negative symptoms were observed in 10-30% of patients. Mortality in patients with schizophrenia was greater than in the general population, with a standardized mortality ratio of 2.58-4.30. Reasons for higher risk of mortality in the schizophrenia population included increased suicide risk, effect of schizophrenia on lifestyle and environment, and presence of comorbidities. Clinical guidelines overall supported the use of second-generation antipsychotics in managing negative symptoms of schizophrenia, although improved therapeutic approaches are needed. Conclusion : Schizophrenia is one of the most common mental illnesses and poses a considerable burden on patients and healthcare resources alike. Negative symptoms are present in many patients and there is an unmet need to improve treatment offerings for negative symptoms beyond the use of second-generation antipsychotics and overall patient outcomes

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

Should science educators deal with the science/religion issue?

I begin by examining the natures of science and religion before looking at the ways in which they relate to one another. I then look at a number of case studies that centre on the relationships between science and religion, including attempts to find mechanisms for divine action in quantum theory and chaos theory, creationism, genetic engineering and the writings of Richard Dawkins. Finally, I consider some of the pedagogical issues that would need to be considered if the science/religion issue is to be addressed in the classroom. I conclude that there are increasing arguments in favour of science educators teaching about the science/religion issue. The principal reason for this is to help students better to learn science. However, such teaching makes greater demands on science educators than has generally been the case. Certain of these demands are identified and some specific suggestions are made as to how a science educator might deal with the science/religion issue. © 2008 Taylor & Francis

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Early Life Child Micronutrient Status, Maternal Reasoning, and a Nurturing Household Environment have Persistent Influences on Child Cognitive Development at Age 5 years : Results from MAL-ED

Funding Information: The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the NIH, and the National Institutes of Health/Fogarty International Center. This work was also supported by the Fogarty International Center, National Institutes of Health (D43-TW009359 to ETR). Author disclosures: BJJM, SAR, LEC, LLP, JCS, BK, RR, RS, ES, LB, ZR, AM, RS, BN, SH, MR, RO, ETR, and LEM-K, no conflicts of interest. Supplemental Tables 1–5 and Supplemental Figures 1–3 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/jn/. Address correspondence to LEM-K (e-mail: [email protected]). Abbreviations used: HOME, Home Observation for Measurement of the Environment inventory; MAL-ED, The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project; TfR, transferrin receptor; WPPSI, Wechsler Preschool Primary Scales of Intelligence.Peer reviewe