Yoko Nomura

Diversified Microbiota of Meconium Is Affected by Maternal Diabetes Status

Objectives This study was aimed to assess the diversity of the meconium microbiome and determine if the bacterial community is affected by maternal diabetes status. Methods The first intestinal discharge (meconium) was collected from 23 newborns stratified by maternal diabetes status: 4 mothers had pre-gestational type 2 diabetes mellitus (DM) including one mother with dizygotic twins, 5 developed gestational diabetes mellitus (GDM) and 13 had no diabetes. The meconium microbiome was profiled using multi-barcode 16S rRNA sequencing followed by taxonomic assignment and diversity analysis. Results All meconium samples were not sterile and contained diversified microbiota. Compared with adult feces, the meconium showed a lower species diversity, higher sample-to-sample variation, and enrichment of Proteobacteria and reduction of Bacteroidetes. Among the meconium samples, the taxonomy analyses suggested that the overall bacterial content significantly differed by maternal diabetes status, with the microbiome of the DM group showing higher alpha-diversity than that of no-diabetes or GDM groups. No global difference was found between babies delivered vaginally versus via Cesarean-section. Regression analysis showed that the most robust predictor for the meconium microbiota composition was the maternal diabetes status that preceded pregnancy. Specifically, Bacteroidetes (phyla) and Parabacteriodes (genus) were enriched in the meconium in the DM group compared to the no-diabetes group. Conclusions Our study provides evidence that meconium contains diversified microbiota and is not affected by the mode of delivery. It also suggests that the meconium microbiome of infants born to mothers with DM is enriched for the same bacterial taxa as those reported in the fecal microbiome of adult DM patients.

Global Methylation in the Placenta and Umbilical Cord Blood From Pregnancies With Maternal Gestational Diabetes, Preeclampsia, and Obesity

Emerging evidence indicates that maternal medical risk during pregnancy, such as gestational diabetes mellitus (GDM), preeclampsia, and obesity, predisposes the offspring to suboptimal development. However, the underlying biological/epigenetic mechanism in utero is still unknown. The current pilot study (N = 50) compared the levels of global methylation in the placenta and umbilical cord blood among women with and without each risk condition (GDM, preeclampsia, and obesity) and explored whether the levels of global methylation were associated with fetal/infant growth. Results show that global methylation levels in the placenta were lower in patients with gestational diabetes (P = .003) and preeclampsia (P = .05) but higher with obesity (P = .01). Suggestive negative associations were found between global methylation level in the placenta and infant body length and head circumference. While preliminary, it is possible that the placenta tissue, but not umbilical cord blood, may be epigenetically programmed by maternal GDM, preeclampsia, and obesity to carry out its own specific functions that influence fetal growth.

Childhood maltreatment and conduct disorder: independent predictors of criminal outcomes in ADHD youth.

OBJECTIVEnChildren with attention-deficit/hyperactivity disorder (ADHD) are at heightened risk for maltreatment in childhood and criminality as they enter into adolescence and early adulthood. Here, we investigated the effect of moderate to severe childhood maltreatment on later criminality among adolescents/young adults diagnosed with ADHD in childhood while accounting for the contributions of other known risk factors such as early conduct disorder (CD).nnnMETHODSnEighty-eight participants from a longitudinal study of children diagnosed with ADHD and screened for comorbid disorders at age 7-11 years were assessed for maltreatment histories at the time of the 10-year adolescent follow-up. Detailed juvenile and adult criminal records were obtained from the New York State Division of Criminal Justice Services approximately 3-years after commencement of the follow-up study. We used regression analyses to determine predictors of adolescent/young adult criminal behavior.nnnRESULTSnModerate to severe childhood maltreatment increased the risk of adolescent/young adult arrest over and above the risk associated with childhood CD, while both childhood maltreatment and childhood CD significantly increased the risk of recidivism. ADHD youth classified as maltreated were three and a half times more likely to be arrested when compared to ADHD youth without a maltreatment classification.nnnCONCLUSIONnWe established maltreatment as a risk factor for criminality in ADHD youth and demonstrated that this relationship was independent of the contributions of CD, and established risk factor for antisocial behavior in this population. The findings highlight the need for maltreatment screening in children with ADHD in order to identify those at heightened risk for criminal activity, and target treatment to improve outcome in this high-risk group of children.

Cannabis-Dependence Risk Relates to Synergism between Neuroticism and Proenkephalin SNPs Associated with Amygdala Gene Expression: Case- Control Study

Background Many young people experiment with cannabis, yet only a subgroup progress to dependence suggesting individual differences that could relate to factors such as genetics and behavioral traits. Dopamine receptor D2 (DRD2) and proenkephalin (PENK) genes have been implicated in animal studies with cannabis exposure. Whether polymorphisms of these genes are associated with cannabis dependence and related behavioral traits is unknown. Methodology/Principal Findings Healthy young adults (18–27 years) with cannabis dependence and without a dependence diagnosis were studied (Nu200a=u200a50/group) in relation to a priori-determined single nucleotide polymorphisms (SNPs) of the DRD2 and PENK genes. Negative affect, Impulsive Risk Taking and Neuroticism-Anxiety temperamental traits, positive and negative reward-learning performance and stop-signal reaction times were examined. The findings replicated the known association between the rs6277 DRD2 SNP and decisions associated with negative reinforcement outcomes. Moreover, PENK variants (rs2576573 and rs2609997) significantly related to Neuroticism and cannabis dependence. Cigarette smoking is common in cannabis users, but it was not associated to PENK SNPs as also validated in another cohort (Nu200a=u200a247 smokers, Nu200a=u200a312 non-smokers). Neuroticism mediated (15.3%–19.5%) the genetic risk to cannabis dependence and interacted with risk SNPs, resulting in a 9-fold increase risk for cannabis dependence. Molecular characterization of the postmortem human brain in a different population revealed an association between PENK SNPs and PENK mRNA expression in the central amygdala nucleus emphasizing the functional relevance of the SNPs in a brain region strongly linked to negative affect. Conclusions/Significance Overall, the findings suggest an important role for Neuroticism as an endophenotype linking PENK polymorphisms to cannabis-dependence vulnerability synergistically amplifying the apparent genetic risk.

Changes in the prevalence of mood and anxiety disorders among male and female current smokers in the United States: 1990-2001.

PURPOSEnThe present study investigated whether the prevalence of mood and anxiety disorders has increased over time among current smokers and whether these trends differ by gender and in comparison with nonsmokers.nnnMETHODSnData were drawn from the National Comorbidity Survey (1990) and the National Comorbidity Survey-Replication (2001), representative samples of the US adult population. Binomial regression analyses were used to determine differences between mood and anxiety disorders among current smokers in 1990 and 2001 and whether these differed by gender and in comparison with those who were former or never current smokers.nnnRESULTSnAny anxiety disorder, panic attacks, panic disorder, social anxiety disorder and dysthymia were all significantly more common among current smokers in 2001 compared with 1990 and except for social anxiety disorder these increases were significantly greater than any trend found in non-smokers. Increases in panic attacks, social anxiety disorder, and dysthymia were more pronounced in female than in male smokers. Major depressive disorder and generalized anxiety disorder were not found to increase over time among smokers.nnnCONCLUSIONSnThe prevalence of several anxiety disorders and dysthymia among current smokers appears to have increased from 1990 to 2001. Future studies are needed to determine whether these trends have continued. If so, interventions aimed at moving the prevalence lower may have limited success if treatment of mental health problems such as anxiety disorders and certain mood disorders are not considered in the development and dissemination of tobacco control programs.

Mitochondrial Gene Expression Profiles Are Associated with Maternal Psychosocial Stress in Pregnancy and Infant Temperament

Background Gene-environment interactions mediate through the placenta and shape the fetal brain development. Between the environmental determinants of the fetal brain, maternal psychosocial stress in pregnancy has been shown to negatively influence the infant temperament development. This in turn may have adverse consequences on the infant neurodevelopment extending throughout the entire life-span. However little is known about the underlying biological mechanisms of the effects of maternal psychosocial stress in pregnancy on infant temperament. Environmental stressors such as maternal psychosocial stress in pregnancy activate the stress response cascade that in turn drives the increase in the cellular energy demand of vital organs with high metabolic rates such as, in pregnancy, the placenta. Key players of the stress response cascade are the mitochondria. Results Here, we tested the expression of all 13 protein-coding genes encoded by the mitochondria in 108 placenta samples from the Stress in Pregnancy birth cohort, a study that aims at determining the influence of in utero exposure to maternal psychosocial stress in pregnancy on infant temperament. We showed that the expression of the protein-coding mitochondrial-encoded gene MT-ND2 was positively associated with indices of maternal psychosocial stress in pregnancy including Prenatal Perceived Stress (β = 0.259; p-regression = 0.004; r2-regression = 0.120), State Anxiety (β = 0.218; p-regression = 0.003; r2-regression = 0.153), Trait Anxiety (β = 0.262; p-regression = 0.003; r2-regression = 0.129) and Pregnancy Anxiety Total (β = 0.208; p-regression = 0.010; r2-regression = 0.103). In the meantime MT-ND2 was negatively associated with the infant temperament indices of Activity Level (β = -0.257; p-regression = 0.008; r2-regression = 0.165) and Smile and Laughter (β = -0.286; p-regression = 0.036; r2-regression = 0.082). Additionally, MT-ND6 was associated with the maternal psychosocial stress in pregnancy index of Prenatal Perceived Stress (β = -0.231; p-regression = 0.004; r2-regression = 0.120), while MT-CO2 was associated with the maternal psychosocial stress in pregnancy indices of State Anxiety (β = 0.206; p-regression = 0.003; r2-regression = 0.153) and Trait Anxiety (β = 0.205; p-regression = 0.003; r2-regression = 0.129). Conclusions Our data support the role of mitochondria in responding to maternal psychosocial stress in pregnancy, as assessed in placenta, while also suggesting an important role for the mitochondria in the infant temperament development.

Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes

PurposePreeclampsia is known to be a leading cause of mortality and morbidity among mothers and their infants. Approximately 3–8% of all pregnancies in the US are complicated by preeclampsia and another 5–7% by hypertensive symptoms. However, less is known about its long-term influence on infant neurobehavioral development. The current review attempts to demonstrate new evidence for imprinting gene dysregulation caused by hypertension, which may explain the link between maternal preeclampsia and neurocognitive dysregulation in offspring.MethodPub Med and Web of Science databases were searched using the terms “preeclampsia,” “gestational hypertension,” “imprinting genes,” “imprinting dysregulation,” and “epigenetic modification,” in order to review the evidence demonstrating associations between preeclampsia and suboptimal child neurodevelopment, and suggest dysregulation of placental genomic imprinting as a potential underlying mechanism.ResultsThe high mortality and morbidity among mothers and fetuses due to preeclampsia is well known, but there is little research on the long-term biological consequences of preeclampsia and resulting hypoxia on the fetal/child neurodevelopment. In the past decade, accumulating evidence from studies that transcend disciplinary boundaries have begun to show that imprinted genes expressed in the placenta might hold clues for a link between preeclampsia and impaired cognitive neurodevelopment. A sudden onset of maternal hypertension detected by the placenta may result in misguided biological programming of the fetus via changes in the epigenome, resulting in suboptimal infant development.ConclusionFurthering our understanding of the molecular and cellular mechanisms through which neurodevelopmental trajectories of the fetus/infant are affected by preeclampsia and hypertension will represent an important first step toward preventing adverse neurodevelopment in infants.

Influences of Maternal Stress during Pregnancy on the Epi/genome: Comparison of Placenta and Umbilical Cord Blood

Background Maternal stress during pregnancy is one of the major adverse environmental factors in utero that is capable of influencing health outcomes of the offspring throughout life. Both genetic and epigenetic processes are susceptible to environmental insults in utero and are potential biomarkers of the experienced environment including maternal stress. Methods We profiled expression level of six genes in hypothalamic pituitary adrenal (HPA) axis functioning (HSD11B2, SLC6A4, NR3C1, NR3C2, CRHR1 and CRHR2), two imprinted genes (IGF2 and H19) and one neurodevelopmental gene (EGR1), from 49 pairs of placenta and umbilical cord blood (UCB) samples from a birth cohort. We also assessed global methylation levels by LUminometric Methylation Assay (LUMA) and methylation at the imprinting control region (ICR) of IGF2/H19. Results Little correlations between paired placenta and UCB were observed except H19 expression (r = 0.31, P = 0.04) and IGF2/H19 ICR methylation (r = 0.43, P = 0.01); gene expression levels were significantly higher (P < 0.001) in placenta than UCB except CRHR1 and CRHR2, which were unexpressed in placenta. Maternal stress correlated higher levels of HPA genes and lower levels of EGR1 and LUMA, but only in placenta. Positive association between maternal stress and IGF2/H19 ICR methylation was present in both placenta and UCB. Conclusions Our findings support the notion that adverse in utero environment, as measured by antenatal maternal stress, depression and anxiety, can be observed in the epi/genome of the relevant tissues, i.e. placenta and UCBs, leading to development of molecular markers for assessing in utero adversities.

Smoking during pregnancy in the United States, 2005–2014: The role of depression

BACKGROUNDnDespite success of public health-oriented tobacco control programs in lowering the smoking prevalence over the past several decades, it is unclear whether similar reductions in smoking have been experienced among pregnant women, especially in vulnerable groups such as those with major depression and/or lower socioeconomic status.nnnOBJECTIVESnThe purpose of this study is to examine the relationship between major depressive episode (MDE) and smoking among pregnant women overall, and by demographics and to estimate changes in the prevalence of cigarette smoking among pregnant women with and without MDE from 2005 to 2014.nnnSTUDY DESIGNnCigarette use among pregnant women with and without MDE was examined using logistic regression models in the National Survey on Drug Use and Health.nnnRESULTSnPrenatal smoking is more common among pregnant women with, compared to without, MDE (32.5% vs. 13.0%; (adjusted OR=2.50 (1.85, 3.40)), and greater disparities were revealed when also considering income, education and race. Over time, smoking during pregnancy increased significantly among women with MDE (35.9% to 38.4%; p=0.02)) and showed a decreasing trend among women without MDE (12.5% to 9.1%; p=0.07) from 2005 to 2014.nnnCONCLUSIONSnOver the past decade, smoking during pregnancy has increased among women experiencing a major depressive episode and is over four times more common among pregnant women with, than without, MDE. Disparities in smoking during pregnancy by MDE status and socioeconomic subgroups appear substantial. Given the multitude of risks associated with both MDE and smoking during the prenatal period, more work targeting this vulnerable and high-risk group is needed.

Short and Long-Term Effects of Compromised Birth Weight, Head Circumference, and Apgar Scores on Neuropsychological Development

Background Low birth weight (LBW, <2500 g) is an adverse perinatal risk that may reflect a poor intrauterine environment. While LBW has been a well-known predictor of physical, neurological, cognitive and psychological deficits later in life, minimal research has been done on small head circumference and low 5 minute Apgar scores, and their association with subsequent developmental abnormalities. Objective The current study aims to demonstrate that small head circumference and low 5-minute Apgar scores are predictors for developmental abnormalities throughout childhood and later. Methods Using a longitudinal design, 2,151 individuals physical, neurological, and cognitive functioning in childhood, as well as psychological functioning in adulthood, was assessed as a function of three perinatal risk factors: LBW, small head circumference and low Apgar scores. Results Similar to findings with LBW, small head circumference or a low Apgar score were associated with increased number of hospital visits (p<0.0001 and p=0.005 respectively) and neurological abnormalities (p<0.0001 and p=0.001 respectively) at age 1. Intelligence quotient (IQ) scores at ages 4 and 7 were significantly lower for those born with small head circumference (p<0.0001) or low Apgar scores (p=0.002). Finally, the incidence of anxiety in adulthood was significantly higher for those born with small head circumference (p=0.03) or low Apgar scores (p=0.004) compared to their counterpart. Conclusion Small head circumference and low a Apgar score are predictors of later physical, neurological, cognitive and psychological abnormalities, and can complement LBW, a more frequently used perinatal risk factor, and thus be used to screen for future developmental deficits, together with LBW.