@misc{SendGillesCoddetal.2018, author = {Send, T. S. and Gilles, M. and Codd, V. and Wolf, I. A. C. and Bardtke, S. and Streit, Fabian and Strohmaier, Jana and Frank, Josef and Schendel, D. and Sutterlin, M. W. and Denniff, M. and Laucht, Manfred and Samani, N. J. and Deuschle, Michael and Rietschel, Marcella and Witt, Stephanie H.}, title = {Telomere length in newborns is related to maternal stress during pregnancy Response}, series = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {43}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, number = {11}, publisher = {Nature Publ. Group}, address = {London}, issn = {0893-133X}, doi = {10.1038/s41386-018-0079-8}, pages = {2164 -- 2164}, year = {2018}, 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{HeinrichBuchmannZohseletal.2015, author = {Heinrich, Angela and Buchmann, Arlette F. and Zohsel, Katrin and Dukal, Helene and Frank, Josef and Treutlein, Jens and Nieratschker, Vanessa and Witt, Stephanie H. and Brandeis, Daniel and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred and Rietschel, Marcella}, title = {Alterations of Glucocorticoid Receptor Gene Methylation in Externalizing Disorders During Childhood and Adolescence}, series = {Behavior genetics : an international journal devoted to research in the inheritance of behavior in animals and man}, volume = {45}, journal = {Behavior genetics : an international journal devoted to research in the inheritance of behavior in animals and man}, number = {5}, publisher = {Springer}, address = {New York}, issn = {0001-8244}, doi = {10.1007/s10519-015-9721-y}, pages = {529 -- 536}, year = {2015}, abstract = {Epigenetic modulations are a hypothesized link between environmental factors and the development of psychiatric disorders. Research has suggested that patients with depression or bipolar disorder exhibit higher methylation levels in the glucocorticoid receptor gene NR3C1. We aimed to investigate whether NR3C1 methylation changes are similarly associated with externalizing disorders such as aggressive behavior and conduct disorder. NR3C1 exon 1F methylation was analyzed in young adults with a lifetime diagnosis of an externalizing disorder (N = 68) or a depressive disorder (N = 27) and healthy controls (N = 124) from the Mannheim Study of Children at Risk. The externalizing disorders group had significantly lower NR3C1 methylation levels than the lifetime depressive disorder group (p = 0.009) and healthy controls (p = 0.001) This report of lower methylation levels in NR3C1 in externalizing disorders may indicate a mechanism through which the differential development of externalizing disorders as opposed to depressive disorders might occur.}, 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{LauchtBeckerFranketal.2008, author = {Laucht, Manfred and Becker, Katja and Frank, Josef and Schmidt, Martin H. and Esser, G{\"u}nter and Treutlein, Jens and Skowronek, Markus H. and Schumann, Gunter}, title = {Genetic variation in dopamine pathways differentially associated with smoking progression in adolescence}, issn = {0890-8567}, doi = {10.1097/Chi.0b013e31816bff77}, year = {2008}, abstract = {Objective: To clarify the nature of the association between dopamine genes and smoking by examining whether genetic variability in components of the dopamine pathway could explain refined phenotypes in adolescent smoking progression. Method: Data are from an ongoing prospective study of the long-term outcome of early risk factors studied since birth. At age 15 years, 220 participants (108 males, 112 females) completed a self-report questionnaire measuring smoking behavior and were genotyped for five dopamine gene variants. Results: Smoking initiation was related to allelic variation in the dopamine D-4 receptor gene (DRD4), whereas smoking continuation and dependence showed association with the dopamine D-2 receptor gene (DRD2). Adolescents with the seven-repeat allele of the common DRD4 exon 3 polymorphism had rates of ever smoking that were significantly higher than in those with other genotypes. Once smoking started, carriers of the T allele of a single nucleotide polymorphism of DRD2 (rs4648317) reported higher rates of current smoking and scored higher on nicotine dependence than their allelic counterparts. Among current smokers, intention to quit was significantly lower in adolescents homozygous for the 10-repeat allele of the common dopamine transporter 3 untranslated region polymorphism. Conclusions: Our results provide preliminary evidence of genetic influences on different stages of smoking and suggest the importance of specific dopamine genes in smoking progression in adolescence.}, language = {en} }