Steven Gregory

Interaction between oxytocin receptor DNA methylation and genotype is associated with risk of postpartum depression in women without depression in pregnancy

Postpartum depression (PPD) affects up to 19% of women, negatively impacting maternal and infant health. Reductions in plasma oxytocin levels have been associated with PPD and heritability studies have established a genetic contribution. Epigenetic regulation of the oxytocin receptor gene (OXTR) has been demonstrated and we hypothesized that individual epigenetic variability at OXTR may impact the development of PPD and that such variability may be central to predicting risk. This case-control study is nested within the Avon Longitudinal Study of Parents and Children and included 269 cases with PPD and 276 controls matched on age group, parity, and presence or absence of depressive symptoms in pregnancy as assessed by the Edinburgh Postnatal Depression Scale. OXTR DNA methylation (CpG site -934) and genotype (rs53576 and rs2254298) were assayed from DNA extracted from blood collected during pregnancy. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of elevated symptoms of PPD with genotype, methylation, and their interaction adjusted for psychosocial factors (n = 500). There was evidence of an interaction between rs53576 and methylation in the OXTR gene amongst women who did not have depression prenatally but developed PPD (p interaction = 0.026, adjusted for covariates, n = 257). Those women with GG genotype showed 2.63 greater odds of PPD for every 10% increase in methylation level (95% CI: 1.37, 5.03), whereas methylation was unrelated to PPD amongst “A” carriers (OR = 1.00, 95% CI: 0.58, 1.73). There was no such interaction among women with PPD and prenatal depression. These data indicate that epigenetic variation that decreases expression of OXTR in a susceptible genotype may play a contributory role in the etiology of PPD.

Personality, Behavior and Environmental Features Associated with OXTR Genetic Variants in British Mothers

Background It is assumed that the oxytocin receptor gene (OXTR) is associated with factors that are related to features of reproduction as well as the currently emerging fields of mood and emotional response. Methods We analysed data from over 8000 mothers who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC). We determined reproductive, emotional and personality differences related to the two SNPs rs53576 and rs2254298 of the oxytocin receptor gene to determine whether there was evidence in this population for: (i) associations with emotional and personality differences, and (ii) behavioural or environmental links with these SNPs using a hypothesis free approach with over 1000 types of exposure. Results Our analyses of 7723 women showed that there were no differences in 11 mood, social or relationship characteristics associated with the rs2254298, and just one with rs53576 (with emotional loneliness) – one statistically significant out of 22 tests is no more than would be expected by chance. There were no interactions with childhood abuse. Using a hypothesis-free approach we found few indicators of environmental or behavioural differences associated with rs2254298, but there was an excess of associations with eating habits with rs53576. The findings included an association with dieting to lose weight, and habits typical of bulimia for the women with GG. The nutrition of the women also showed negative associations of the GG genotype with 13 nutrients, including vitamins D, B12 and retinol, and intake of calcium, potassium and iodine. Conclusions We conclude that this large database of pregnant women was unable to provide confirmation of the types of personality associated with these two OXTR SNPs, but we have shown some evidence of eating differences in those with GG on rs53576. Confirmation of our hypothesis free associations using other data sets is important.

Grand-maternal smoking in pregnancy and grandchild’s autistic traits and diagnosed autism

Although there is considerable research into the genetic background of autism spectrum disorders, environmental factors are likely to contribute to the variation in prevalence over time. Rodent experiments indicate that environmental exposures can have effects on subsequent generations, and human studies indicate that parental prenatal exposures may play a part in developmental variation. Here we use the Avon Longitudinal Study of Parents and Children (ALSPAC) to test the hypothesis that if the mother or father (F1) had been exposed to their own mother’s (F0) smoking during pregnancy, the offspring (F2) would be at increased risk of autism. We find an association between maternal grandmother smoking in pregnancy and grand daughters having adverse scores in Social Communication and Repetitive Behaviour measures that are independently predictive of diagnosed autism. In line with this, we show an association with actual diagnosis of autism in her grandchildren. Paternal grandmothers smoking in pregnancy showed no associations.

The antecedents of women's external locus of control: Associations with characteristics of their parents and their early childhood.

Locus of control (LOC) measures individuals’ expectancies regarding their ability to affect what happens to them based on how they behave. The more they believe their behaviour has something to do with what happens to them the more internal they are. In contrast the more they perceive that what happens to them is beyond their control and determined by luck, fate, chance or powerful others the more external they are. Copious research findings suggest that external LOC (ELOC) is associated with many adverse personal, social, academic and health outcomes. In spite of its importance in so many areas of human behaviour relatively little is known about the features of the early background of individuals that contributes to these expectancies. This is the first in a number of studies that will suggest possible antecedents and consequences of having a high ELOC. The study takes advantage of the data collected in the Avon Longitudinal Study of Parents and Children (ALSPAC), which started by studying pregnancies in 1991–1992 of residents in an area of south-west England. Over 12000 of the women who enrolled during pregnancy completed a set of questions in mid-pregnancy from which an LOC score was computed. ELOC was defined as a score greater than the median. The relationships with characteristics of the women’s parents and her early childhood (<6 years) are considered first as unadjusted odds ratios and then as adjusted after analysis using hierarchical sets of stepwise logistic regressions. The relative contributions to the women’s ELOC was measured using a goodness-of-fit (GOF) measure. The analyses demonstrated the independent importance of maternal and paternal backgrounds as well as features of her early childhood (<6 years). The final model identified nine independent features (each with P < 0.0001): year of birth of her mother, maternal and paternal education levels, father smoked, mother smoked when pregnant, year of birth of study woman, the number of older siblings she had, whether her father was absent during this period, and whether she spent her childhood in the study area. In conclusion, the woman’s LOC appears to be independently influenced by a number of characteristics which may give clues as to possible mechanisms—and how internality may be supported in the future. Subsequent papers will assess both whether features of later childhood influence the woman’s LOC and whether the LOC of men in the study have similar antecedents.

Prenatal mercury exposure and offspring behaviour in childhood and adolescence

Highlights • There is controversy as to whether prenatal mercury levels are associated with adverse child behaviour, especially if the mother does not eat fish.• This study compares the relationship between maternal total blood mercury in the first half of pregnancy and child behaviour at seven time points.• No evidence was found to suggest that the mercury level was associated with adverse behaviour, whether or not the mother ate fish.

Parental, prenatal, and neonatal associations with ball skills at age 8 using an exposome approach

There is little consistency in the literature concerning factors that influence motor coordination in children. A hypothesis-free “exposome” approach was used with 7359 children using longitudinal information covering 3 generations in regard to throwing a ball accurately at age 7 years. The analyses showed an independent robust negative association with mother’s unhappiness in her midchildhood (6-11 years). No such association was present for study fathers. The offspring of parents who described themselves as having poor eyesight had poorer ability. This hypothesis-free approach has identified a strong negative association with an unhappy childhood. Future studies of this cohort will be used to determine whether the mechanism is manifest through differing parenting skills, or a biological mechanism reflecting epigenetic effects.

Parental External Locus of Control in Pregnancy Is Associated with Subsequent Teacher Ratings of Negative Behavior in Primary School: Findings from a British Birth Cohort

The purpose of the present study was to examine whether parents’ locus of control (LOC) obtained before the birth of their child predicts the child’s behavior at school in School Years 3 (ages 7–8) and 6 (ages 10–11). A modified version of the adult Nowicki–Strickland internal–external locus of control scale was completed by mothers and fathers in their own home during pregnancy. Externality was defined as a score greater than the median and internality as equal to, or less than, the median. Outcomes were the five individual subscales and the total difficulties of Goodman’s strengths and difficulties’ questionnaire completed by the children’s class teachers at the end of School Years 3 and 6. As predicted, it was found that the greater the presence of externality in the parents, the greater the increased risk of the child’s adverse behavior as rated by teachers. The risk was generally greatest if both parents were external and lowest if both were internal. There was a consistent relationship at both Year 3 and Year 6 between maternal externality in pregnancy and children’s emotional difficulties. However, for other behaviors, the pattern of associations varied depending on whether the mother or father was external, the type of adverse behavior, and the School Year in which children were assessed. Prenatal parental externality appears to be significantly associated with a variety of children’s negative behaviors. Of note was the finding that fathers’ as well as mothers’ LOC was important in determining children’s outcomes. Implications of the complexity of the results for the role parents may play in children’s personality and adjustment are discussed.

The Prevalence of Tympanic Membrane and Related Middle Ear Pathology in Children: A Large Longitudinal Cohort Study Followed From Birth to Age Ten

Objective: To record with video-otoscopy the appearance of the tympanic membranes of a cross section of children aged 9 to 10 years. Study Design: Cross-sectional study nested within an established longitudinal study of childhood development, the Avon Longitudinal Study of Parents and Children. Setting: South West England, U.K. Participants: Approximately 6908 of 7261 children with ages ranging from 105 to 140 months born between April 1, 1991, and December 31, 1992, were examined by trained technicians with video-otoscopy. Main Outcome Measures: Two photographs were taken of each childs tympanic membranes to show the features of the pars tensa and the pars flaccida. Results: In just less than three quarters of the children, both ears were normal. Retraction of the pars flaccida was present in 9.6% of children, and that of the pars tensa was present in 7.9%. Most of these changes were mild with few severe retractions. There were 15 cases of overt or suspected cholesteatoma. Conclusion: The tympanic membrane changes reflect most of the middle ear disease seen in 9- to 10-year-old children. The prevalence is low, and few children have serious disease at this stage.

Events associated with stability and change in adult locus of control orientation over a six-year period

Although locus of control (LOC) has been the focus of thousands of studies we know little about how or if it changes over time and what is associated with change. Our lack of knowledge stems in part from the past use of cross-sectional and not longitudinal methodologies to study small numbers of participants from non-representative populations. The purpose of the present study was to use a longitudinal design with a large representative population to provide relevant information concerning the stability and change of adult LOC. Before the birth of their child, and again six years later, mothers and their partners participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) completed LOC tests and structured stressful events surveys. Analyses revealed that stresses experienced in relationships with spouses, friends and family, financial stability and job security, and illness/smoking were associated with changes in LOC. Results suggest substantial variation of LOC within spousal/parent dyads and moderate stability of LOC over time for both men and women. Stressors associated with change in LOC may be possible candidates when considering interventions to modify LOC expectancies.

Prenatal Internal Locus of Control Is Positively Associated with Offspring IQ, Mediated through Parenting Behavior, Prenatal Lifestyle and Social Circumstances

Locus of control (LOC) is a measure that identifies the likelihood as to whether an individual considers what happens to him is largely a matter of luck or fate (known as externally oriented) or whether it is something that the individual can influence (internality). Here we have used data collected as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine the associations between the mothers’ LOC orientation before the birth of the child and her child’s cognition measured at age 8. Using results from 6801 children we show that maternal internal LOC is associated with increased ability in offspring IQ, as measured using the WISC, with children of internally oriented mothers having an advantage of approximately 7 IQ points at age 8. As a sensitivity analysis we used the IQ test results of a sample of 986 preschool children tested using the WPSSI at age 4. A similar advantage was found among the offspring of the internally oriented mothers. We investigated mechanistic explanations for these results firstly by determining the extent to which three separate sets of factors known to be influenced by the LOC orientation might explain these findings. We showed that (a) perinatal life-style exposures, (b) parenting attitudes and strategies and (c) socio-economic circumstances, largely explain the mechanism through which the internality of the mother influences the cognition of the child. Similar effects were found using the smaller sample tested at age 4. The results indicate that efforts made to foster internality in adolescents and young adults prior to parenthood may result in improvements in the cognitive development of the next generation. Intervention studies are urgently needed.