TY - JOUR A1 - Gilles, Maria A1 - Otto, Henrike A1 - Wolf, Isabell A. C. A1 - Scharnholz, Barbara A1 - Peus, Verena A1 - Schredl, Michael A1 - Suetterlin, Marc W. A1 - Witt, Stephanie H. A1 - Rietschel, Marcella A1 - Laucht, Manfred A1 - Deuschle, Michael T1 - Maternal hypothalamus-pituitary-adrenal (HPA) system activity and stress measures at birth JF - Psychoneuroendocrinology N2 - Background: Prenatal maternal stress might be a risk for the developing fetus and may have long-lasting effects on child and adult vulnerability to somatic and psychiatric disease. Over-exposure of the unborn to excess glucocorticoids and subsequent alteration of fetal development is hypothesized to be one of the key mechanisms linking prenatal stress with negative child outcome. Methods: In this prospective longitudinal study, mothers-to-be (n = 405) in late pregnancy (36.8 +/- 1.9 weeks of gestational age) and their singleton neonates were studied. We investigated the impact of different prenatal stress indices derived from six stress variables (perceived stress, specific prenatal worries, negative life events, symptoms of depression, trait anxiety, neuroticism) and diurnal maternal saliva cortisol secretion on gestational age and anthropometric measures at birth. KW - Early life stress KW - Gestational age KW - Anthropometric measures at birth KW - Cortisol KW - Prenatal distress KW - Pregnancy Y1 - 2018 U6 - https://doi.org/10.1016/j.psyneuen.2018.04.022 SN - 0306-4530 VL - 94 SP - 152 EP - 161 PB - Elsevier CY - Oxford ER - TY - GEN A1 - Send, T. S. A1 - Gilles, M. A1 - Codd, V. A1 - Wolf, I. A. C. A1 - Bardtke, S. A1 - Streit, Fabian A1 - Strohmaier, Jana A1 - Frank, Josef A1 - Schendel, D. A1 - Sutterlin, M. W. A1 - Denniff, M. A1 - Laucht, Manfred A1 - Samani, N. J. A1 - Deuschle, Michael A1 - Rietschel, Marcella A1 - Witt, Stephanie H. T1 - Telomere length in newborns is related to maternal stress during pregnancy Response T2 - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology KW - Predictive markers KW - Risk factors Y1 - 2018 U6 - https://doi.org/10.1038/s41386-018-0079-8 SN - 0893-133X SN - 1740-634X VL - 43 IS - 11 SP - 2164 EP - 2164 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Send, Tabea Sarah A1 - Bardtke, Svenja A1 - Gilles, Maria A1 - Wolf, Isabella Germaine A1 - Sütterlin, Marc W. A1 - Kirschbaum, Clemens A1 - Laucht, Manfred A1 - Witt, Stephanie H. A1 - Rietschel, Marcella A1 - Streit, Fabian A1 - Deuschle, Michael T1 - Stress reactivity in preschool-aged children BT - Evaluation of a social stress paradigm and investigation of the impact of prenatal maternal stress JF - Psychoneuroendocrinology N2 - Prenatal maternal stress is an established risk factor for somatic and psychological health of the offspring. A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in offspring has been suggested as an important mechanism. However, the impact of prenatal stress on stress reactivity in preschool-aged children is not yet well understood. This is partly due to the fact that for this age group there is no stress test as well established as for older children and adults. In the present work a previously published stress test (Kryski et al., 2011) was evaluated in a large sample of 45-month-old children (n = 339). Furthermore, the relation between measures of prenatal maternal stress and cortisol reactivity was investigated. Prenatal stress was defined as psychopathology (self-report available for n = 339; expert-rating available for a subsample of n = 246) and perceived stress (n = 244) during pregnancy. The stress paradigm elicited significant increases in salivary cortisol 30 and 40 min after the test, and 60.8% of the children were classified as responders. Lower cortisol levels after the stress test were observed in the group of children with prenatal stress defined as maternal psychopathology (both self-reported and expert-rated). Maternal perceived stress as a continuous measure was not significantly associated with cortisol levels. However, when comparing children in the highest quartile of maternal perceived stress to all other children, significantly lower cortisol values were observed in the prenatally stressed group. The present study confirms the paradigm by Kryski et al. as an effective stress test for preschool-aged children. Moreover, it provides further evidence that prenatal stress impacts HPA axis reactivity. Future studies should target the timing, nature, and intensity of prenatal stressors and their effect on the stress response in offspring at different developmental stages. KW - Stress test KW - Children KW - Prenatal stress KW - Cortisol KW - HPA axis reactivity KW - Psychopathology Y1 - 2018 U6 - https://doi.org/10.1016/j.psyneuen.2018.11.002 SN - 0306-4530 VL - 101 SP - 223 EP - 231 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Witt, Stephanie H. A1 - Frank, Josef A1 - Gilles, Maria A1 - Lang, Maren A1 - Treutlein, Jens A1 - Streit, Fabian A1 - Wolf, Isabell A. C. A1 - Peus, Verena A1 - Scharnholz, Barbara A1 - Send, Tabea S. A1 - Heilmann-Heimbach, Stefanie A1 - Sivalingam, Sugirthan A1 - Dukal, Helene A1 - Strohmaier, Jana A1 - Sütterlin, Marc A1 - Arloth, Janine A1 - Laucht, Manfred A1 - Nöthen, Markus M. A1 - Deuschle, Michael A1 - Rietschel, Marcella T1 - Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation JF - BMC genomics N2 - Background: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. Methods: Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. Results: Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top "smoking methylation pattern" genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. Conclusion: The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight. KW - DNA methylation KW - Smoking KW - Birth weight KW - Mediation analysis Y1 - 2018 U6 - https://doi.org/10.1186/s12864-018-4652-7 SN - 1471-2164 VL - 19 PB - BMC CY - London ER - TY - JOUR A1 - Wolf, Isabell Ann-Cathrin A1 - Gilles, Maria A1 - Peus, Verena A1 - Scharnholz, Barbara A1 - Seibert, Julia A1 - Jennen-Steinmetz, Christine A1 - Krumm, Bertram A1 - Rietschel, Marcella A1 - Deuschle, Michael A1 - Laucht, Manfred T1 - Impact of prenatal stress on mother-infant dyadic behavior during the still-face paradigm JF - Borderline Personality Disorder and Emotion Dysregulation : the official journal of the National Education Alliance for Borderline Personality Disorder (NEA.BPD) and Dachverband Dialektisch Behaviorale Therapie (DDBT) N2 - Background: Mother-infant interaction provides important training for the infant’s ability to cope with stress and the development of resilience. Prenatal stress (PS) and its impact on the offspring’s development have long been a focus of stress research, with studies highlighting both harmful and beneficial effects. The aim of the current study was to examine the possible influence of both psychological stress and hypothalamic-pituitary-adrenal (HPA) axis activity during pregnancy with mother-child dyadic behavior following stress exposure. Methods: The behavior of 164 mother-infant dyads during the still-face situation was filmed at six months postpartum and coded into three dyadic patterns: 1) both positive, 2) infant protesting-mother positive, and 3) infant protesting-mother negative. PS exposure was assessed prenatally according to psychological measures (i.e., psychopathological, perceived and psychosocial PS; n = 164) and HPA axis activity measures (maternal salivary cortisol, i.e., cortisol decline and area under the curve with respect to ground (AUCg); n = 134). Results: Mother-infant dyads in both the high- and low-stress groups showed decreasing positive and increasing negative dyadic behavior in the reunion episode, which is associated with the well-known “still-face” and “carry-over” effect. Furthermore, mother-infant dyads with higher psychosocial PS exhibited significantly more positive dyadic behavior than the low psychosocial PS group in the first play episode, but not in the reunion episode. Similarly, mother-infant dyads with high HPA axis activity (i.e. high AUCg) but steeper diurnal cortisol decline (i.e. cortisol decline) displayed significantly less negative behavior in the reunion episode than dyads with low HPA axis activity. No significant results were found for psychopathological stress and perceived stress. Conclusions: The results suggest a beneficial effect of higher psychosocial PS and higher prenatal maternal HPA axis activity in late gestation, which is in line with “stress inoculation” theories. KW - Prenatal stress KW - Face-to-face still-face paradigm KW - Resilience KW - Psychosocial stress KW - Cortisol Y1 - 2018 U6 - https://doi.org/10.1186/s40479-018-0078-8 SN - 2051-6673 VL - 5 PB - BioMed Central CY - London ER -