<i>BNDF </i>methylation in mothers and newborns is associated with maternal exposure to war trauma

Abstract Background The BDNF gene codes for brain-derived neurotrophic factor, a growth factor involved in neural development, cell differentiation, and synaptic plasticity. Present in both the brain and periphery, BDNF plays critical roles throughout the body and is essential for placental and fetal development. Rodent studies show that early life stress, including prenatal stress, broadly alters BDNF methylation, with presumed changes in gene expression. No studies have assessed prenatal exposure to maternal traumatic stress and BDNF methylation in humans. This study examined associations of prenatal exposure to maternal stress and BDNF methylation at CpG sites across the BDNF gene. Results Among 24 mothers and newborns in the eastern Democratic Republic of Congo, a region with extreme conflict and violence to women, maternal experiences of war trauma and chronic stress were associated with BDNF methylation in umbilical cord blood, placental tissue, and maternal venous blood. Associations of maternal stress and BDNF methylation showed high tissue specificity. The majority of significant associations were observed in putative transcription factor binding regions. Conclusions This is the first study in humans to examine BDNF methylation in relation to prenatal exposure to maternal stress in three tissues simultaneously and the first in any mammalian species to report associations of prenatal stress and BDNF methylation in placental tissue. The findings add to the growing body of evidence highlighting the importance of considering epigenetic effects when examining the impacts of trauma and stress, not only for adults but also for offspring exposed via effects transmitted before birth

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate &lt;0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P &lt; 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Validation of the adherence evaluation of osteoporosis treatment (ADEOS) questionnaire for osteoporotic post-menopausal women

SUMMARY: We developed and validated a specific 12-item questionnaire to evaluate adherence to oral antiresorptive medication by post-menopausal osteoporotic women in everyday practice. Over the following 9 months, an index of ≤16 was associated with an increase in the risk of treatment discontinuation of 1.69 and of 2.10 for new patients who had started treatment within the previous year. INTRODUCTION: Adherence to medication in osteoporosis is poor. The goal of this study was to develop and validate a disease-specific questionnaire to evaluate adherence to treatment of women with post-menopausal osteoporosis taking oral antiresorptive medication. METHODS: A prototype adherence questionnaire with 45 items developed from patient interview, literature review, and physician opinion was evaluated in a sample of 350 post-menopausal women with osteoporosis treated in primary care. Item responses were matched against scores on the Morisky Medication Adherence Scale (MMAS). The most discriminant items were retained in the final questionnaire. Concurrent and predictive validity were assessed. RESULTS: Twelve items were associated with MMAS score at a probability level of 0.05. These were retained in the final questionnaire which provided an adherence index ranging from 0 to 22. An index of ≥20 was associated with a high probability of persistence and an index ≤ 16 with a high probability of treatment discontinuation in the following 9 months. CONCLUSIONS: The ADEOS-12 is a simple patient-reported measure to determine adherence to osteoporosis treatments with good concurrent and discriminant validity. This is the first disease-specific adherence measure to have been developed for osteoporosis

Parent perceptions of the quality of life of pet dogs living with neuro-typically developing and neuro-atypically developing children: an exploratory study

There is growing scientific and societal recognition of the role that pet dogs can play in healthy development of children; both those who are neuro-typically developing and those who live with a neuro-developmental disorder, such as autism or attention deficit hyperactivity disorder. However, little attention has been paid to how living with children positively and negatively affects quality of life of a pet dog. In this exploratory study we conducted semi-structured interviews with parents of neuro-typically developing children (n = 18) and those with a neuro-developmental disorder (n = 18) who owned a pet dog, until no new factors were identified. Living with children brought potentially positive benefits to the dog’s life including: imposition of a routine, participation in recreational activities and the development of a strong bond between the child and the dog. The importance of maintaining a routine was particularly prevalent in families with children with neuro-developmental disorders. Potential negative factors included having to cope with child meltdowns and tantrums, over stimulation from child visitors, harsh contact and rough and tumble play with the child. The regularity and intensity of meltdowns and tantrums was particularly evident in responses from parents with children with a neuro-developmental disorder. However, child visitors and rough play and contact were mentioned similarly across the groups. Protective factors included having a safe haven for the dog to escape to, parent’s awareness of stress signs and child education in dog-interaction. Parents were also asked to complete a stress response scale to provide an initial quantitative comparison of stress responses between dogs living with the two family-types. Parents with neuro-typically developing children more frequently observed their dog rapidly running away from a situation and less frequently observed their dog widening their eyes, than parents with children with a neuro-developmental disorder. We propose the development of a stress audit based on the findings reported here, to prevent potential dangerous situations, which may lead to dog bites and dog relinquishment and allow owners to maximise the benefits of dog ownership

Pathway based analysis of genotypes in relation to alcohol dependence

We introduce a method for detecting variants in several genes of related function with small effect on a phenotype of interest. Our method uses logistic regression to test whether multiple alleles within a functional set have significantly higher than expected predictive value, even though none individually may have strong individual effects. We illustrate this method by testing seven gene sets (including 48 genes), from a study with1350 single nucleotide polymorphisms in 130 addiction candidate genes studied in a sample of 575 alcohol dependence (AD) cases and 530 controls. We conclude that AD is related to variation in genes participating in Glutamate and GABA signaling, as has been reported elsewhere, and in stress response pathways, but not with genes in several other systems implicated in other drugs of abuse