TY - JOUR A1 - Send, Tabea A1 - Bardtke, S. A1 - Gilles, M. A1 - Wolf, I. A. C. A1 - Sütterlin, Marc Wolf A1 - Wudy, S. A. A1 - Wang, R. A1 - Laucht, Manfred A1 - Witt, Stephanie H. A1 - Rietschel, Marcella A1 - Streit, Fabian A1 - Deuschle, Michael T1 - Prenatal maternal stress is associated with lower cortisol and cortisone levels in the first morning urine of 45-month-old children JF - Psychoneuroendocrinology N2 - Prenatal stress (PS) has been related to altered hypothalamic-pituitary-adrenal (HPA) axis activity later in life. So far, studies in children assessing HPA axis functioning have focused on salivary cortisol, reflecting daytime activity. The present work is part of a prospective study and aims to extend knowledge about the association between PS and HPA axis regulation in children. To do so, we investigated cortisol, cortisone, and the ratio cortisone/(cortisone + cortisol) in the first morning urine of 45-month-old children in relation to several measures of maternal stress during pregnancy. Urinary cortisol and cortisone were measured by online turbulent flow chromatography coupled with high performance liquid chromatography-tandem mass spectrometry. PS was defined as: perceived stress for aim 1 (Perceived Stress Scale; n = 280); presence of self-reported (n = 371) and expert-rated psychopathology for aim 2 (Mini International Neuropsychiatric Interview; n = 281); continuous measures of anxiety and depression for exploratory aim 3 (State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale; n = 280). The ratio cortisone/(cortisone + cortisol) as a global marker for the balance between the enzymes metabolizing cortisol to cortisone and vice versa (11 beta-hydroxysteroid dehydrogenases type 1 and 2; 11 beta-HSD1 and 2) was not associated with any measure of maternal PS (aims 1-3). The present study provides insight into possible programming effects of PS on nocturnal HPA axis activity and a proxy of 11 beta-HSD in a large sample. The results suggest that the nocturnal rate of cortisol production is lower in children exposed to PS, but do not support the hypothesis of divergent 11 beta-HSD activity. KW - Prenatal stress KW - Cortisol KW - Cortisone KW - HPA axis KW - Perceived stress KW - Psychopathology Y1 - 2019 U6 - https://doi.org/10.1016/j.psyneuen.2019.01.017 SN - 0306-4530 VL - 103 SP - 219 EP - 224 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 - 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 - 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 - Send, Tabea Sarah A1 - Gilles, Maria A1 - Codd, Veryan A1 - Wolf, Isabell A1 - Bardtke, Svenja A1 - Streit, Fabian A1 - Strohmaier, Jana A1 - Frank, Josef A1 - Schendel, Darja A1 - Suetterlin, Mark W. A1 - Denniff, Matthew A1 - Laucht, Manfred A1 - Samani, Nilesh J. A1 - Deuschle, Michael A1 - Rietschel, Marcella A1 - Witt, Stephanie H. T1 - Telomere Length in Newborns is Related to Maternal Stress During Pregnancy JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology N2 - Telomere length (TL) is a marker of biological aging, and numerous studies have shown associations between TL and somatic or psychiatric disorders. Research also indicates an association between maternal stress during pregnancy and TL in the offspring. The present study investigated possible associations between TL and: (1) maternal perceived stress during pregnancy; (2) a maternal lifetime history of psychiatric disorder (lifetime PD); and (3) paternal age. TL was analyzed in 319 newborns and 318 mothers from a predominantly Caucasian sample (n= 273 Caucasian newborns and n= 274 Caucasian mothers). Two key findings were observed. First, maternal perceived stress during pregnancy was associated with shorter telomeres in newborns but not with maternal TL. Second, maternal lifetime PD was associated with shorter maternal telomeres, but not with TL in newborns. Paternal age was not associated with TL in newborns. The finding that maternal stress during pregnancy is associated with shorter telomeres in newborns supports the results of smaller previous studies. The fact that a relation between maternal prenatal stress and TL was observed in the offspring but not in mothers may be attributable to a high vulnerability to stress during intrauterine development of a maturing organism. To our knowledge, this is the largest study to date to show that maternal stress during pregnancy but not maternal lifetime PD is associated with shorter telomeres in the offspring. Y1 - 2017 U6 - https://doi.org/10.1038/npp.2017.73 SN - 0893-133X SN - 1740-634X VL - 42 SP - 2407 EP - 2413 PB - Nature Publ. Group CY - London ER -