AVPR1A variation is linked to gray matter covariation in the social brain network of chimpanzees

The vasopressin system has been implicated in the regulation of social behavior and cognition in humans, nonhuman primates and other social mammals. In chimpanzees, polymorphisms in the vasopressin V1a receptor gene (AVPR1A) have been associated with social dimensions of personality, as well as to responses to sociocommunicative cues and mirror self‐recognition. Despite evidence of this association with social cognition and behavior, there is little research on the neuroanatomical correlates of AVPR1A variation. In the current study, we tested the association between AVPR1A polymorphisms in the RS3 promotor region and gray matter covariation in chimpanzees using magnetic resonance imaging and source‐based morphometry. The analysis identified 13 independent brain components, three of which differed significantly in covariation between the two AVPR1A genotypes (DupB?/? and DupB+/?; P < .05). DupB+/? chimpanzees showed greater covariation in gray matter in the premotor and prefrontal cortex, basal forebrain, lunate and cingulate cortex, and lesser gray matter covariation in the superior temporal sulcus and postcentral sulcus. Some of these regions were previously found to differ in vasopressin and oxytocin neural fibers between nonhuman primates, and in AVPR1A gene expression in humans with different RS3 alleles. This is the first report of an association between AVPR1A and gray matter covariation in nonhuman primates, and specifically links an AVPR1A polymorphism to structural variation in the social brain network. These results further affirm the value of chimpanzees as a model species for investigating the relationship between genetic variation, brain structure and social cognition with relevance to psychiatric disorders, including autism.     

Thinking and doing: the effects of dopamine and oxytocin genes and executive function on mothering behaviours

Animal and human studies suggest that initial expression of maternal behaviour depends on oxytocin and dopamine systems. However, the mechanism by which these systems affect parenting behaviours and the timing of these effects are not well understood. This article explores the role of mothers' executive function in mediating the relation between oxytocin and dopamine gene variants and maternal responsiveness at 48 months post‐partum. Participants (n = 157) were mothers recruited in the Maternal Adversity, Vulnerability and Neurodevelopment Study, which assesses longitudinally two cohorts of mothers and children in Canada. We examined single nucleotide polymorphisms (SNPs) related to the dopamine and oxytocin systems (DRD1 rs686, DRD1 rs265976, OXTR rs237885 and OXTR rs2254298), assessed mothers' decision‐making at 48 months using the Cambridge Neurological Automated Testing Battery (CANTAB) and evaluated maternal responsiveness from videotaped interactions during the Etch‐A‐Sketch co‐operation task. Mediation analyses showed that OXTR rs2254298 A‐carriers had an indirect effect on positive parenting which was mediated by mothers' performance on decision‐making task (estimate = 0.115, P < 0.005), while OXTR rs2254298 A‐carriers had both direct and indirect effects on physically controlling parenting, also mediated through enhanced performance on decision‐making (estimate = ?0.059, P < 0.005). Dopamine SNPs were not associated with any measure of executive function or parenting (all P > 0.05). While oxytocin has previously been associated with only the early onset of maternal behaviour, we show that an OXTR polymorphism is involved in maternal behaviour at 48 months post‐partum through mothers' executive function. This research highlights the importance of the oxytocin system to maternal parenting beyond infancy.     

Maternal feeding strategies, child eating behaviors, and child BMI in low-income African-American preschoolers

Objective: To test the hypothesis that low‐income African‐American preschool children would have a higher BMI if their mothers reported greater “restriction” and “control” in feeding and if mothers reported that children showed greater “food responsiveness” and “desire to drink.” In addition, to test whether higher maternal “pressure to eat” would be associated with lower child BMI. Research Methods and Procedures: A questionnaire was completed by 296 low‐income African‐American mothers of preschool children. It assessed three constructs on maternal feeding strategies (“restriction,” “pressure to eat,” and “control”) and two on child eating behaviors (“food responsiveness” and “desire to drink”). Children's BMI was measured, and mothers’ BMI was self‐reported. Results: The mean (standard deviation) BMI z‐score of the children was 0.34 (1.5), and 44% of the mothers were obese (BMI ≥30 kg/m²). Only maternal “pressure to eat” had a significant overall association with child BMI z‐score (r = ?0.16, p < 0.01). Both maternal “restriction” and “control” were positively associated with children's BMI z‐score in the case of obese mothers (r = 0.20, p = 0.03 and r = 0.24, p = 0.007, respectively), but this was not so in the case of non‐obese mothers (r = ?0.16, p = 0.05 and r = ?0.07, p = 0.39, respectively). Discussion: Among low‐income African Americans, the positive association between maternal restriction and control in feeding and their preschoolers’ BMI was limited to obese mothers. Relations between parent feeding strategies and child weight status in this population may differ on the basis of maternal weight status.     

Genetic variation in oxytocin rs2740210 and early adversity associated with postpartum depression and breastfeeding duration

Mothers vary in duration of breastfeeding. These individual differences are related to a variety of demographic and individual maternal factors including maternal hormones, mood and early experiences. However, little is known about the role of genetic factors. We studied single‐nucleotide polymorphisms (SNPs) in the OXT peptide gene (rs2740210; rs4813627) and the OXT receptor gene (OXTR rs237885) in two samples of mothers from the Maternal adversity, Vulnerability and Neurodevelopment study (MAVAN), a multicenter (Hamilton and Montreal, Canada) study following mothers and their children from pregnancy until 7 years of age. Data from the Hamilton site was the primary sample (n = 201) and data from Montreal was the replication sample (n = 151). Breastfeeding duration, maternal mood (measured by the CES‐D scale) and early life adversity (measured by the CTQ scale) were established during 12 months postpartum. In our primary sample, polymorphisms in OXT rs2740210, but not the other SNPs, interacted with early life adversity to predict variation in breastfeeding duration (overall F_8,125 = 2.361, P = 0.021; interaction effect b = ?8.12, t = ?2.3, P = 0.023) and depression (overall F_8,118 = 5.751, P ≤ 0.001; interaction effect b = 6.06, t = 3.13, P = 0.002). A moderated mediation model showed that higher levels of depression mediated the inverse relation of high levels of early life adversity to breastfeeding duration, but only in women possessing the CC genotype [effect a′ = ?3.3401, 95% confidence interval (CI) = ?7.9466 to ?0.0015] of the OXT SNP and not in women with the AA/AC genotype (a′ = ?1.2942, ns). The latter findings (moderated mediation model) were replicated in our Montreal sample (a′ = ?0.277, 95% CI = ?0.7987 to ?0.0348 for CC; a′ = ?0.1820, ns for AA/AC) .     

Genetic variants in oxytocin receptor and arginine-vasopressin receptor 1A are associated with the neural correlates of maternal and paternal affection towards their child

There is extensive evidence in animal studies, particularly in vole species (Microtus), that oxytocin (OT) receptor and arginine-vasopressin (AVP) receptor 1a is critical for the regulation of maternal and paternal behavior, respectively. Human studies have gained insight into the relationship between both hormone receptor gene variants and behavior, but not between the variants and the underlying brain activity. To study this, we investigated the association between neural activation of the anterior prefrontal cortex (APFC) in mothers and fathers in response to their child smiling video stimuli to induce the positive affect related to attachment with their child, and genetic variants of OT receptor (OXTR) and AVP receptor 1A (AVPR1A). Overall, 43 mothers and 41 fathers participated, and each parent's child smiling was video recorded. Participants were then genotyped and underwent near-infrared spectroscopy to measure neural activation of the APFC while observing their own child smiling compared with an unfamiliar child. We found that the right inferior APFC was activated in response to child video stimuli in mothers and differential hemispheric activation of the inferior APFC in OXTR rs2254298-G/G mothers compared with -A carrier mothers, but not in fathers. Furthermore, we found a difference in the left inferior APFC activation between AVPR1A RS3-non-334 and -334 carrier fathers, but not mothers. Our results indicate a sex-dependent association between the genetic variants and the inferior APFC activations of maternal and paternal positive affect, analogous to the results reported in voles.     

Epigenetic variation in OPRM1 gene in opioid‐exposed mother‐infant dyads

Neonatal abstinence syndrome (NAS) due to in‐utero opioid exposure has significant variability of severity. Preliminary studies have suggested that epigenetic variation within the μ‐opioid receptor (OPRM1) gene impacts NAS. We aimed to determine if DNA methylation in OPRM1 within opioid‐exposed mother‐infant dyads is associated with differences in NAS severity in an independent cohort. Full‐term opioid‐exposed newborns and their mothers (N = 68 pairs) were studied. A DNA sample was obtained and then assessed for level of DNA methylation at 20 CpG sites within the OPRM1 promoter region by next‐generation sequencing. Infants were monitored for NAS and treated with replacement opioids according to institutional protocol. The association between DNA methylation level at each CpG site with NAS outcome measures was evaluated using linear and logistic regression models. Higher methylation levels within the infants at the ?18 (11.4% vs 4.4%, P = .0001), ?14 (46.1% vs 24.0%, P = .002) and +23 (26.3% vs 12.9%, P = .008) CpG sites were associated with higher rates of infant pharmacologic treatment. Higher levels of methylation within the mothers at the ?169 (R = 0.43, P = .008), ?152 (R = 0.40, P = .002) and +84 (R = 0.44, P = .006) sites were associated point‐wise with longer infant length of stay. Maternal associations remained significant point‐wise for ?169 (β = 0.07, P = .007) and on an experiment‐wise level for +84 (β = ?0.10, P = .003) using regression models. These results suggest an association of higher levels of OPRM1 methylation at specific CpG sites and increased NAS severity, replicating prior findings. These findings have important implications for personalized treatment regimens for infants at high risk for severe NAS.     

Association between the oxytocin receptor (OXTR) gene and children's social cognition at 18 months

At 18 months, children engage in a variety of social behaviors that reflect their nascent ability to understand the intentions of other people (e.g. joint attention, empathy, cooperation and self‐recognition). Although numerous contextual factors have been shown to predict social cognition in young children, the genetic underpinnings of social‐cognitive traits has been understudied in this age group. Owing to the known effects of oxytocin on adult social cognition and psychopathology, this study hypothesized that variability in the oxytocin receptor gene (OXTR) would be associated with social cognition in children at 18 months. Participants consisted of 350 children (182 males; 168 females) who were part of an ongoing longitudinal study that aimed to assess environmental and genetic contributions to children's cognitive and socio‐emotional functioning. At 18 months, social cognition was measured using previously validated and developmentally sensitive tasks assessing children's joint attention, empathy, cooperation and self‐recognition. Five potentially functional OXTR variants were genotyped: rs1042778, rs2254298, rs11131149, rs237897 and rs237899. A family‐based association design was used to control for population admixture and stratification, and additional non‐genomic covariates were controlled. Results showed that variability in rs11131149 was significantly associated with social cognition (P = 0.009), with more copies of the major allele related to higher social cognition, and more copies of the minor (risk) allele associated with lower social cognition. A haplotype consisting of rs11131149–rs2254298 was also associated with social cognition (P = 0.020). Implications for normative and pathological development are discussed, and key areas for future research are proposed.     

Arginine vasopressin 1a receptor gene and maternal behavior: evidence of association and moderation

This study examined associations among maternal sensitivity, mothers' early adversity and the Arginine Vasopressin 1a Receptor (AVPR1A) gene. Early adversity in mothers' background has been found to be associated with lower maternal sensitivity. Animal literature suggests that variation in the AVPR1A gene is associated with parenting quality. The goal of the study was to examine the role of the AVPR1A gene in maternal sensitivity, especially under conditions of high early adversity. Participants included 151 Caucasian women from a community sample. The women were videotaped in their home while interacting separately with two of their children (target child = 18 months, older sibling <6 years). Evidence was found for an association between the AVPR1A gene and maternal sensitivity. Mothers with two copies of the long RS3 alleles were less sensitive than mothers with one or zero copies of the long alleles. This association was strongest under conditions of high maternal early adversity.     

Oxytocin receptor and vasopressin receptor 1a genes are respectively associated with emotional and cognitive empathy

Empathy is the ability to recognize and share in the emotions of others. It can be considered a multifaceted concept with cognitive and emotional aspects. Little is known regarding the underlying neurochemistry of empathy and in the current study we used a neurogenetic approach to explore possible brain neurotransmitter pathways contributing to cognitive and emotional empathy. Both the oxytocin receptor (OXTR) and the arginine vasopressin receptor 1a (AVPR1a) genes contribute to social cognition in both animals and humans and hence are prominent candidates for contributing to empathy. The following research examined the associations between polymorphisms in these two genes and individual differences in emotional and cognitive empathy in a sample of 367 young adults. Intriguingly, we found that emotional empathy was associated solely with OXTR, whereas cognitive empathy was associated solely with AVPR1a. Moreover, no interaction was observed between the two genes and measures of empathy. The current findings contribute to our understanding of the distinct neurogenetic pathways involved in cognitive and emotional empathy and underscore the pervasive role of both oxytocin and vasopressin in modulating human emotions.     

Molecular Variation in AVP and AVPR1a in New World Monkeys (Primates,Platyrrhini): Evolution and Implications for Social Monogamy

The neurohypophysial hormone arginine vasopressin (AVP) plays important roles in fluid regulation and vascular resistance. Differences in AVP receptor expression, particularly mediated through variation in the noncoding promoter region of the primary receptor for AVP (AVPR1a), may play a role in social phenotypes, particularly social monogamy, in rodents and humans. Among primates, social monogamy is rare, but is common among New World monkeys (NWM). AVP is a nonapeptide and generally conserved among eutherian mammals, although a recent paper demonstrated that some NWM species possess a novel form of the related neuropeptide hormone, oxytocin. We therefore characterized variation in the AVP and AVPR1a genes in 22 species representing every genus in the three major platyrrhine families (Cebidae, Atelidae and Pitheciidae). For AVP, a total of 16 synonymous substitutions were detected in 15 NWM species. No non-synonymous substitutions were noted, hence, AVP is conserved in NWM. By contrast, relative to the human AVPR1a, 66 predicted amino acids (AA) substitutions were identified in NWM. The AVPR1a N-terminus (ligand binding domain), third intracellular (G-protein binding domain), and C-terminus were variable among species. Complex evolution of AVPR1a is also apparent in NWM. A molecular phylogenetic tree inferred from AVPR1a coding sequences revealed some consensus taxonomic separation by families, but also a mixed group composed of genera from all three families. The overall dN/dS ratio of AVPR1a was 0.11, but signals of positive selection in distinct AVPR1a regions were observed, including the N-terminus, in which we identified six potential positive selection sites. AA substitutions at positions 241, 319, 399 and 409 occurred uniquely in marmosets and tamarins. Our results enhance the appreciation of genetic diversity in the mammalian AVP/AVPR1a system, and set the stage for molecular modeling of the neurohypophyseal hormones and social behavior in primates.     

The influence of AVPR1A genotype on individual differences in behaviors during a mirror self‐recognition task in chimpanzees (Pan troglodytes)

The mark/rouge test has been used to assess mirror self‐recognition (MSR) in many species. Despite consistent evidence of MSR in great apes, genetic or non‐genetic factors may account for the individual differences in behavioral responses that have been reported. We examined whether vasopressin receptor gene (AVPR1A) polymorphisms are associated with MSR‐related behaviors in chimpanzees since vasopressin has been implicated in the development and evolution of complex social relations and cognition and chimpanzees are polymorphic for the presence of the RS3‐containing DupB region. We compared a sample of DupB+/? and DupB?/? chimpanzees on a mark test to assess its role on social behavior toward a mirror. Chimpanzees were administered two, 10‐min sessions where frequencies of mirror‐guided self‐directed behaviors, contingent actions and other social behaviors were recorded. Approximately one‐third showed evidence of MSR and these individuals exhibited more mirror‐guided self‐exploratory behaviors and mouth contingent actions than chimpanzees not classified as passers. Moreover, DupB+/? males exhibited more scratching and agonistic behaviors than other male and female cohorts. Our findings support previous studies demonstrating individual differences in MSR abilities in chimpanzees and suggest that AVPR1A partly explains individual differences in MSR by influencing the behavioral reactions of chimpanzees in front of a mirror.     

Dopamine receptors D1 and D2 are related to observed maternal behavior

The dopamine pathway and especially the dopamine receptors 1 and 2 (DRD1 and DRD2) are implicated in the regulation of mothering in rats. Evidence for this in humans is lacking. Here, we show that genetic variation in both DRD1 and DRD2 genes in a sample of 187 Caucasian mothers predicts variation in distinct maternal behaviors during a 30-min mother-infant interaction at 6 months postpartum. Two DRD1 single-nucleotide polymorphisms (SNPs rs265981 and rs686) significantly associated with maternal orienting away from the infant (P = 0.002 and P = 0.003, respectively), as did DRD1 haplotypes (P = 0.03). Two DRD2 SNPs (rs1799732 and rs6277) significantly associated with maternal infant-directed vocalizing (P = 0.001 and P = 0.04, respectively), as did DRD2 haplotypes (P = 0.01). We present evidence for heterosis in DRD1 where heterozygote mothers orient away from their infants significantly less than either homozygote group. Our findings provide important evidence that genetic variation in receptors critical for mothering in non-human species also affect human maternal behaviors. The findings also highlight the importance of exploring multiple dimensions of the complex human mothering phenotype.     

Impact of Childhood Adversity and Vasopressin receptor 1a Variation on Social Interaction in Adulthood: A Cross-Sectional Study

Background

Arginine vasopressin (AVP) plays a role in social behavior, through receptor AVPR1A. The promoter polymorphism AVPR1A RS3 has been associated with human social behaviors, and with acute response to stress. Here, the relationships between AVPR1A RS3, early-life stressors, and social interaction in adulthood were explored.

Methods

Adult individuals from a Swedish population-based cohort (n = 1871) were assessed for self-reported availability of social integration and social attachment and for experience of childhood adversities. Their DNA samples were genotyped for the microsatellite AVPR1A RS3.

Results

Among males, particularly those homozygous for the long alleles of AVPR1A RS3 were vulnerable to childhood adversity for their social attachment in adulthood. A similar vulnerability to childhood adversity among long allele carriers was found on adulthood social integration, but here both males and females were influenced.

Limitation

Data were self-reported and childhood adversity data were retrospective.

Conclusions

Early-life stress influenced the relationship between AVPR1A genetic variants and social interaction. For social attachment, AVPR1A was of importance in males only. The findings add to previous reports on higher acute vulnerability to stress in persons with long AVPR1A RS3 alleles and increased AVP levels.     

Body mass, DRD4, physical activity, sedentary behavior, and family socioeconomic status: the add health study

Objective: To investigate the joint role of the 48‐base pair repeat polymorphism of the dopamine receptor 4 gene (DRD4) and environmental factors in body mass variation among an ethnically diverse sample of U.S. adolescents and young adults. Research Methods and Procedures: Approximately 2600 adolescent and young adults in the National Longitudinal Study of Adolescent Health (Add Health) who provided DNA measures and measures of height and weight were included in the analysis. Mixed regression modeling was used to investigate the effects of the 7R/7R and any5R variants in the DRD4 gene simultaneously with the effects of physical activity (PA), sedentary behavior (SB), and family socioeconomic status (SES) on body mass variation. European Americans, African Americans, and Hispanic Americans were modeled separately. Results and Discussion: Both the 7R/7R and any5R genotypes of the DRD4 gene were associated with age‐ and sex‐specific BMI percentile score (BMI‐P) based on the Centers for Disease Control and Prevention/National Center for Health Statistics 2000 reference curves among African Americans and only among African Americans (N = 413) 20 years old or younger. Neither genetic variants are associated with the BMI measure among white (N = 1386) and Hispanic‐American (N = 331) adolescents. The presence of the 7R/7R genotype was associated with a reduction of 15.1 in BMI percentile (p = 0.005), and the presence of any5R was associated with an increase of 15.5 in BMI percentile (p = 0.003), after adjusting for PA, SB, and family SES. Neither PA nor SB as measured in Add Health is importantly associated with BMI‐P, suggesting a complex relationship between body mass and PA/SB among adolescents and young adults. Family SES is negatively related to BMI‐P in the European‐American sample.     

AVPR1A Sequence Variation in Monogamous Owl Monkeys (Aotus azarai) and Its Implications for the Evolution of Platyrrhine Social Behavior

The arginine vasopressin V1a receptor gene (AVPR1A) has been implicated in increased partner preference and pair bonding behavior in mammalian lineages. This observation is of considerable importance for studies of social monogamy, which only appears in a small subset of primate taxa, including the Argentinean owl monkey (Aotus azarai). Thus, to investigate the possible influence of AVPR1A on the evolution of social behavior in owl monkeys, we sequenced this locus in a wild population from the Gran Chaco. We also assessed the interspecific variation of AVPR1A in platyrrhine species that represent a set of phylogenetically and behaviorally disparate taxa. The resulting data revealed A. azarai to have a unique genic structure for AVPR1A that varies in coding sequence and microsatellite repeat content relative to other primate and mammalian species. Specifically, one repetitive region that has been the focus in studies of human AVPR1A diversity, “RS3,” is completely absent in A. azarai and all other platyrrhines examined. This finding suggests that, if AVPR1A modulates behavior in owl monkeys and other neotropical primates, it does so independent of this region. These observations have also provided clues about the process by which the range of social behavior in the Order Primates evolved through lineage-specific neurogenetic variation.     

Prediction of Leisure‐time Physical Activity Among Obese Individuals

The aims of this study were to identify (i) what cognitions predict leisure‐time physical activity and (ii) the moderators of cognition‐behavior relationships among obese individuals. A sample of 91 adults (BMI ≥30 kg/m²) completed a baseline questionnaire assessing variables of the theory of planned behavior (TPB). Biological measures and socio‐demographic variables were also obtained. Behavior was assessed 3 months later. Multiple hierarchical regression analyses indicated that significant variables predicting behavior were past behavior (β = 0.39; P = 0.0001), intention (β = 0.27; P = 0.03), and the interaction term “perceived behavioral control (PBC) × perceived built environment” (β = 0.17; P = 0.05). The PBC‐behavior relation was better when the built environment was perceived as favorable to physical activity. The model explained 41% of variance in behavior. The determinants explaining intention were PBC (β = 0.55; P < 0.0001), anticipated regret (β = 0.26; P = 0.0007), and past behavior (β = 0.22; P = 0.005), accounting for 59% of variance. Participation in leisure‐time physical activity is explained primarily by a person's intentions to perform this behavior. The results also suggest that people are more able to translate their perception of control into action if they perceive the built environment as favorable, although this additional gain in prediction is small relative to intention. Nonetheless, both cognitions and aspects of the built environment should be given consideration in the promotion of leisure‐time physical activity among obese individuals.     

Programming social behavior by the maternal fragile X protein

The developing fetus and neonate are highly sensitive to maternal environment. Besides the well‐documented effects of maternal stress, nutrition and infections, maternal mutations, by altering the fetal, perinatal and/or early postnatal environment, can impact the behavior of genetically normal offspring. Mutation/premutation in the X‐linked FMR1 (encoding the translational regulator FMRP) in females, although primarily responsible for causing fragile X syndrome (FXS) in their children, may also elicit such maternal effects. We showed that a deficit in maternal FMRP in mice results in hyperactivity in the genetically normal offspring. To test if maternal FMRP has a broader intergenerational effect, we measured social behavior, a core dimension of neurodevelopmental disorders, in offspring of FMRP‐deficient dams. We found that male offspring of Fmr1^+/? mothers, independent of their own Fmr1 genotype, exhibit increased approach and reduced avoidance toward conspecific strangers, reminiscent of ‘indiscriminate friendliness’ or the lack of stranger anxiety, diagnosed in neglected children and in patients with Asperger's and Williams syndrome. Furthermore, social interaction failed to activate mesolimbic/amygdala regions, encoding social aversion, in these mice, providing a neurobiological basis for the behavioral abnormality. This work identifies a novel role for FMRP that extends its function beyond the well‐established genetic function into intergenerational non‐genetic inheritance/programming of social behavior and the corresponding neuronal circuit. As FXS premutation and some psychiatric conditions that can be associated with reduced FMRP expression are more prevalent in mothers than full FMR1 mutation, our findings potentially broaden the significance of FMRP‐dependent programming of social behavior beyond the FXS population.     

Maternal inflammatory diet and adverse pregnancy outcomes: Circulating cytokines and genomic imprinting as potential regulators?

Excessive inflammation during pregnancy alters homeostatic mechanisms of the developing fetus and has been linked to adverse pregnancy outcomes. An anti-inflammatory diet could be a promising avenue to combat the pro-inflammatory state of pregnancy, particularly in obese women, but we lack mechanistic data linking this dietary pattern during pregnancy to inflammation and birth outcomes. In an ethnically diverse cohort of 1057 mother-child pairs, we estimated the relationships between dietary inflammatory potential [measured via the energy-adjusted dietary inflammatory index (E-DII?)] and birth outcomes overall, as well as by offspring sex and maternal pre-pregnancy body mass index (BMI). In a subset of women, we also explored associations between E-DII, circulating cytokines (n = 105), and offspring methylation (n = 338) as potential modulators of these relationships using linear regression. Adjusted regression models revealed that women with pro-inflammatory diets had elevated rates of preterm birth among female offspring [β = ?0.22, standard error (SE) = 0.07, P<0.01], but not male offspring (β=0.09, SE = 0.06, P<0.12) (P_interaction = 0.003). Similarly, we observed pro-inflammatory diets were associated with higher rates of caesarean delivery among obese women (β = 0.17, SE = 0.08, P = 0.03), but not among women with BMI <25 kg/m² (P_interaction = 0.02). We observed consistent inverse associations between maternal inflammatory cytokine concentrations (IL-12, IL-17, IL-4, IL-6, and TNFα) and lower methylation at the MEG3 regulatory sequence (P<0.05); however, results did not support the link between maternal E-DII and circulating cytokines. We replicate work by others on the association between maternal inflammatory diet and adverse pregnancy outcomes and provide the first empirical evidence supporting the inverse association between circulating cytokine concentrations and offspring methylation.     

Maternal Social Disadvantage and Newborn Telomere Length in Archived Dried Blood Spots from the Michigan Neonatal Biobank

Telomeres are the protective caps at the ends of eukaryotic chromosomes. Short telomere length is associated with morbidity and mortality among adults and may mark the biological impact of social experiences. Using archived dried blood spots from the Michigan Neonatal Biobank, this study examined markers of maternal social disadvantage (educational attainment, receipt of public assistance, marital status, and race/ethnicity) from linked birth certificates as predictors of telomere length at birth in a sample of 192 singleton neonates born to non-Hispanic black, non-Hispanic white, and Latina mothers aged 20–35 years. Consistent with two recent studies in newborns, but counter to the idea that maternal social disadvantage is associated with shorter offspring telomere length, we found that infants born to black mothers had longer telomeres than those born to white mothers (b = 0.12, SE = 0.06, p = .05). However, black/white differences in newborn telomere length varied by receipt of public assistance. Among newborns whose mothers received WIC and/or Medicaid, there were no significant black/white differences in telomere length (b = 0.09, SE = 0.08, p = .25). In contrast, among those whose mothers did not receive public assistance—just 6 out of 69 infants born to black mothers versus 41 out of 69 infants born to white mothers—we found that babies born to black mothers had longer telomere length than babies born to white mothers (b = 0.37, SE = 0.16, p = .03). The interaction between black race/ethnicity and receipt of public assistance did not reach the conventional threshold for statistical significance (b = ?0.22, SE = 0.15, p = .13), suggesting that this finding may be due to chance. No other markers of maternal social disadvantage were related to infant telomere length. Although replication of these results in a larger sample with more infants born to black mothers with relatively high socioeconomic status is needed, this study offers preliminary support for the hypothesis that race/ethnic differences in newborn telomere length depend on social context.