TY  - JOUR
A1  - Heinrich, Angela
A1  - Buchmann, Arlette F.
A1  - Zohsel, Katrin
A1  - Dukal, Helene
A1  - Frank, Josef
A1  - Treutlein, Jens
A1  - Nieratschker, Vanessa
A1  - Witt, Stephanie H.
A1  - Brandeis, Daniel
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Laucht, Manfred
A1  - Rietschel, Marcella
T1  - Alterations of Glucocorticoid Receptor Gene Methylation in Externalizing Disorders During Childhood and Adolescence
JF  - Behavior genetics : an international journal devoted to research in the inheritance of behavior in animals and man
N2  - 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.
KW  - Epigenetic
KW  - Glucocorticoid receptor
KW  - Methylation
KW  - Externalizing disorders
KW  - Adolescents
Y1  - 2015
U6  - https://doi.org/10.1007/s10519-015-9721-y
SN  - 0001-8244
SN  - 1573-3297
VL  - 45
IS  - 5
SP  - 529
EP  - 536
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Laucht, Manfred
A1  - Becker, Katja
A1  - Frank, Josef
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Treutlein, Jens
A1  - Skowronek, Markus H.
A1  - Schumann, Gunter
T1  - Genetic variation in dopamine pathways differentially associated with smoking progression in adolescence
N2  - 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.
Y1  - 2008
U6  - https://doi.org/10.1097/Chi.0b013e31816bff77
SN  - 0890-8567
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  - 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  - 
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  -