@article{WolfGillesPeusetal.2018, author = {Wolf, Isabell Ann-Cathrin and Gilles, Maria and Peus, Verena and Scharnholz, Barbara and Seibert, Julia and Jennen-Steinmetz, Christine and Krumm, Bertram and Rietschel, Marcella and Deuschle, Michael and Laucht, Manfred}, title = {Impact of prenatal stress on mother-infant dyadic behavior during the still-face paradigm}, series = {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)}, volume = {5}, journal = {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)}, publisher = {BioMed Central}, address = {London}, issn = {2051-6673}, doi = {10.1186/s40479-018-0078-8}, pages = {13}, year = {2018}, abstract = {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.}, language = {en} } @article{WolfGillesPeusetal.2017, author = {Wolf, Isabell Ann-Cathrin and Gilles, Maria and Peus, Verena and Scharnholz, Barbara and Seibert, Julia and Jennen-Steinmetz, Christine and Krumm, Bertram and Deuschle, Michael and Laucht, Manfred}, title = {Impact of prenatal stress on the dyadic behavior of mothers and their 6-month-old infants during a play situation: role of different dimensions of stress}, series = {Journal of neural transmission}, volume = {124}, journal = {Journal of neural transmission}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-017-1770-3}, pages = {1251 -- 1260}, year = {2017}, language = {en} } @article{WittFrankGillesetal.2018, author = {Witt, Stephanie H. and Frank, Josef and Gilles, Maria and Lang, Maren and Treutlein, Jens and Streit, Fabian and Wolf, Isabell A. C. and Peus, Verena and Scharnholz, Barbara and Send, Tabea S. and Heilmann-Heimbach, Stefanie and Sivalingam, Sugirthan and Dukal, Helene and Strohmaier, Jana and S{\"u}tterlin, Marc and Arloth, Janine and Laucht, Manfred and N{\"o}then, Markus M. and Deuschle, Michael and Rietschel, Marcella}, title = {Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation}, series = {BMC genomics}, volume = {19}, journal = {BMC genomics}, publisher = {BMC}, address = {London}, issn = {1471-2164}, doi = {10.1186/s12864-018-4652-7}, pages = {10}, year = {2018}, abstract = {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.}, language = {en} } @article{SendGillesCoddetal.2017, author = {Send, Tabea Sarah and Gilles, Maria and Codd, Veryan and Wolf, Isabell and Bardtke, Svenja and Streit, Fabian and Strohmaier, Jana and Frank, Josef and Schendel, Darja and Suetterlin, Mark W. and Denniff, Matthew and Laucht, Manfred and Samani, Nilesh J. and Deuschle, Michael and Rietschel, Marcella and Witt, Stephanie H.}, title = {Telomere Length in Newborns is Related to Maternal Stress During Pregnancy}, series = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {42}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, publisher = {Nature Publ. Group}, address = {London}, issn = {0893-133X}, doi = {10.1038/npp.2017.73}, pages = {2407 -- 2413}, year = {2017}, abstract = {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.}, language = {en} } @article{SendBardtkeGillesetal.2018, author = {Send, Tabea Sarah and Bardtke, Svenja and Gilles, Maria and Wolf, Isabella Germaine and S{\"u}tterlin, Marc W. and Kirschbaum, Clemens and Laucht, Manfred and Witt, Stephanie H. and Rietschel, Marcella and Streit, Fabian and Deuschle, Michael}, title = {Stress reactivity in preschool-aged children}, series = {Psychoneuroendocrinology}, volume = {101}, journal = {Psychoneuroendocrinology}, publisher = {Elsevier}, address = {Oxford}, issn = {0306-4530}, doi = {10.1016/j.psyneuen.2018.11.002}, pages = {223 -- 231}, year = {2018}, abstract = {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.}, language = {en} } @article{SendBardtkeGillesetal.2019, author = {Send, Tabea and Bardtke, S. and Gilles, M. and Wolf, I. A. C. and S{\"u}tterlin, Marc Wolf and Wudy, S. A. and Wang, R. and Laucht, Manfred and Witt, Stephanie H. and Rietschel, Marcella and Streit, Fabian and Deuschle, Michael}, title = {Prenatal maternal stress is associated with lower cortisol and cortisone levels in the first morning urine of 45-month-old children}, series = {Psychoneuroendocrinology}, volume = {103}, journal = {Psychoneuroendocrinology}, publisher = {Elsevier}, address = {Oxford}, issn = {0306-4530}, doi = {10.1016/j.psyneuen.2019.01.017}, pages = {219 -- 224}, year = {2019}, abstract = {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.}, language = {en} } @article{PaslakisBuchmannWestphaletal.2014, author = {Paslakis, Georgios and Buchmann, Arlette F. and Westphal, Sabine and Banaschewski, Tobias and Hohm, Erika and Zimmermann, Ulrich S. and Laucht, Manfred and Deuschle, Michael}, title = {Intrauterine exposure to cigarette smoke is associated with increased ghrelin concentrations in adulthood}, series = {Neuroendocrinology : international journal for basic and clinical studies on neuroendocrine relationships}, volume = {99}, journal = {Neuroendocrinology : international journal for basic and clinical studies on neuroendocrine relationships}, number = {2}, publisher = {Karger}, address = {Basel}, issn = {0028-3835}, doi = {10.1159/000363325}, pages = {123 -- 129}, year = {2014}, abstract = {Background: The appetite-stimulating hormone ghrelin is a fundamental regulator of human energy metabolism. A series of studies support the notion that long-term appetite and weight regulation may be already programmed in early life and it could be demonstrated that the intrauterine environment affects the ghrelin system of the offspring. Animal studies have also shown that intrauterine programming of orexigenic systems persists even until adolescence/adulthood. Methods: We hypothesized that plasma ghrelin concentrations in adulthood may be associated with the intrauterine exposure to cigarette smoke. We examined this hypothesis in a sample of 19-year-olds followed up since birth in the framework of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study of the long-term outcome of early risk factors. Results: As a main finding, we found that ghrelin plasma concentrations in young adults who had been exposed to cigarette smoke in utero were significantly higher than in those without prenatal smoke exposure. Moreover, individuals with intrauterine nicotine exposure showed a significantly higher prevalence of own smoking habits and lower educational status compared to those in the group without exposure. Conclusion: Smoking during pregnancy may be considered as an adverse intrauterine influence that may alter the endocrine-metabolic status of the offspring even until early adulthood.}, language = {en} } @article{GillesOttoWolfetal.2018, author = {Gilles, Maria and Otto, Henrike and Wolf, Isabell A. C. and Scharnholz, Barbara and Peus, Verena and Schredl, Michael and Suetterlin, Marc W. and Witt, Stephanie H. and Rietschel, Marcella and Laucht, Manfred and Deuschle, Michael}, title = {Maternal hypothalamus-pituitary-adrenal (HPA) system activity and stress measures at birth}, series = {Psychoneuroendocrinology}, volume = {94}, journal = {Psychoneuroendocrinology}, publisher = {Elsevier}, address = {Oxford}, issn = {0306-4530}, doi = {10.1016/j.psyneuen.2018.04.022}, pages = {152 -- 161}, year = {2018}, abstract = {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.}, language = {en} } @article{BuchmannKopfWestphaletal.2010, author = {Buchmann, Arlette F. and Kopf, Daniel and Westphal, Sabine and Lederbogen, Florian and Banaschewski, Tobias and Esser, G{\"u}nter and Schmidt, Martin H. and Zimmermann, Ulrich S. and Laucht, Manfred and Deuschle, Michael}, title = {Impact of early parental child-rearing behavior on young adults' cardiometabolic risk profile : a prospective study}, issn = {0033-3174}, doi = {10.1097/Psy.0b013e3181c88343}, year = {2010}, abstract = {Objective: To examine prospectively whether early parental child-rearing behavior is a predictor of cardiometabolic outcome in young adulthood when other potential risk factors are controlled. Metabolic factors associated with increased risk for cardiovascular disease have been found to vary, depending on lifestyle as well as genetic predisposition. Moreover, there is evidence suggesting that environmental conditions, such as stress in pre- and postnatal life, may have a sustained impact on an individual's metabolic risk profile. Methods: Participants were drawn from a prospective, epidemiological, cohort study followed up from birth into young adulthood. Parent interviews and behavioral observations at the age of 3 months were conducted to assess child-rearing practices and mother-infant interaction in the home setting and in the laboratory. In 279 participants, anthropometric characteristics, low-density lipoprotein and high-density lipoprotein cholesterol, apolipoproteins, and triglycerides were recorded at age 19 years. In addition, structured interviews were administered to the young adults to assess indicators of current lifestyle and education. Results: Adverse early-life interaction experiences were significantly associated with lower levels of high- density lipoprotein cholesterol and apolipoprotein A1 in young adulthood. Current lifestyle variables and level of education did not account for this effect, although habitual smoking and alcohol consumption also contributed significantly to cardiometabolic outcomes. Conclusions: These findings suggest that early parental child-rearing behavior may predict health outcome in later life through its impact on metabolic parameters in adulthood.}, language = {en} } @article{BuchmannHellwegRietscheletal.2013, author = {Buchmann, Arlette F. and Hellweg, Rainer and Rietschel, Marcella and Treutlein, Jens and Witt, Stephanie H. and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred and Deuschle, Michael}, title = {BDNF Val 66 Met and 5-HTTLPR genotype moderate the impact of early psychosocial adversity on plasma brain-derived neurotrophic factor and depressive symptoms - a prospective study}, series = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {23}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, number = {8}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0924-977X}, doi = {10.1016/j.euroneuro.2012.09.003}, pages = {902 -- 909}, year = {2013}, abstract = {Recent studies have emphasized an important role for neurotrophins, such as brain-derived neurotrophic factor (BDNF), in regulating the plasticity of neural circuits involved in the pathophysiology of stress-related diseases. The aim of the present study was to examine the interplay of the BDNF Val(66)Met and the serotonin transporter promoter (5-HTTLPR) polymorphisms in moderating the impact of early-life adversity on BDNF plasma concentration and depressive symptoms. Participants were taken from an epidemiological cohort study following the long-term outcome of early risk factors from birth into young adulthood. In 259 individuals (119 males, 140 females), genotyped for the BDNF Val(66)Met and the 5-HTTLPR polymorphisms, plasma BDNF was assessed at the age of 19 years. In addition, participants completed the Beck Depression Inventory (BDI). Early adversity was determined according to a family adversity index assessed at 3 months of age. Results indicated that individuals homozygous for both the BDNF Val and the 5-HTTLPR L allele showed significantly reduced BDNF levels following exposure to high adversity. In contrast, BDNF levels appeared to be unaffected by early psychosocial adversity in carriers of the BDNF Met or the 5-HTTLPR S allele. While the former group appeared to be most susceptible to depressive symptoms, the impact of early adversity was less pronounced in the latter group. This is the first preliminary evidence indicating that early-life adverse experiences may have lasting sequelae for plasma BDNF levels in humans, highlighting that the susceptibility to this effect is moderated by BDNF Val(66)Met and 5-HTTLPR genotype.}, language = {en} }