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  - Witt, Stephanie H.
A1  - Buchmann, Arlette F.
A1  - Blomeyer, Dorothea
A1  - Nieratschker, Vanessa
A1  - Treutlein, Jens
A1  - Esser, Günter
A1  - Schmidt, Martin H.
A1  - Bidlingmaier, Martin
A1  - Wiedemann, Klaus
A1  - Rietschel, Marcella
A1  - Laucht, Manfred
A1  - Wuest, Stefan
A1  - Zimmermann, Ulrich S.
T1  - An interaction between a neuropeptide Y gene polymorphism and early adversity modulates endocrine stress responses
JF  - Psychoneuroendocrinology
N2  - Interindividual variability in the regulation of the human stress system accounts for a part of the individual's liability to stress-related diseases. These differences are influenced by environmental and genetic factors. Early childhood adversity is a well-studied environmental factor affecting an individual's stress response which has been shown to be modulated by gene environment interaction (GxE). Neuropeptide Y (NPY) plays a role in stress regulation and genetic variation in NPY may influence stress responses. In this study, we analyzed the association of a common variant in the NPY gene promoter, rs16147, with cortisol and ACTH responses to acute psychosocial stress in young adults from the Mannheim Study of Children at Risk (MARS), an ongoing epidemiological cohort study following the outcome of early adversity from birth into adulthood. We found evidence of a GxE interaction between rs16147 and early adversity significantly affecting HPA axis responses to acute psychosocial stress. These findings suggest that the neurobiological mechanisms linking early adverse experience and later neuroendocrine stress regulation are modulated by a gene variant whose functional relevance is documented by increasing convergent evidence from in vitro, animal and human studies.
KW  - GxE interaction
KW  - Stress
KW  - HPA
KW  - Neuropeptide Y
KW  - Early adversity
Y1  - 2011
U6  - https://doi.org/10.1016/j.psyneuen.2010.12.015
SN  - 0306-4530
VL  - 36
IS  - 7
SP  - 1010
EP  - 1020
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Schmid, Brigitte
A1  - Blomeyer, Dorothea
A1  - Becker, Katja
A1  - Treutlein, Jens
A1  - Zimmermann, Ulrich S.
A1  - Buchmann, Arlette F.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Rietschel, Marcella
A1  - Laucht, Manfred
T1  - The interaction between the dopamine transporter gene and age at onset in relation to tobacco and alcohol use among 19-year-olds
N2  - Recent evidence suggests that heterogeneity in the age at onset could explain the inconsistent findings of association studies relating the dopamine transporter (DAT1) gene with alcohol and nicotine consumption. The aim of this study was to examine interactions between two DAT1 polymorphisms and different initiation ages with regard to alcohol and tobacco consumption levels and dependence. Two hundred and ninety-one young adults (135 males, 156 females) participating in the Mannheim Study of Children at Risk were genotyped for the 40-bp variable number of tandem repeats (VNTR) and rs27072 polymorphisms of DAT1. Age at initiation was assessed at age 15 and 19 years. Information about current alcohol and tobacco consumption was obtained at age 19 years using self-report measures and structured interviews. Results suggest that age at onset of intensive consumption moderated the association of the DAT1 gene with early adult substance use and dependence, revealing a DAT1 effect only among individuals homozygous for the 10r allele of the 40-bp VNTR who had started daily smoking or being intoxicated early in life. Equally, carriers of the T allele of the rs27072 polymorphism reporting an early age at first intoxication showed higher current alcohol consumption at age 19 years. In contrast, no interaction between rs27072 and the age at first cigarette with regard to later smoking was observed. These findings provide evidence that the DAT1 gene interacts with an early heavy or regular drug exposure of the maturing adolescent brain to predict substance (ab)use in young adulthood. Further studies are required to confirm these findings.
Y1  - 2009
UR  - http://www3.interscience.wiley.com/cgi-bin/issn?DESCRIPTOR=PRINTISSN&VALUE=1355-6215
U6  - https://doi.org/10.1111/j.1369-1600.2009.00171.x
SN  - 1355-6215
ER  - 
TY  - JOUR
A1  - Laucht, Manfred
A1  - Treutlein, Jens
A1  - Schmid, Brigitte
A1  - Blomeyer, Dorothea
A1  - Becker, Katja
A1  - Buchmann, Arlette F.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Jennen-Steinmetz, Christine
A1  - Rietschel, Marcella
A1  - Zimmermann, Ulrich S.
A1  - Banaschewski, Tobias
T1  - Impact of psychosocial adversity on alcohol intake in young adults : moderation by the LL genotype of the serotonin transporter polymorphism
N2  - Background: Evidence from animal studies supports a role for serotonin transporter gene promoter polymorphism (5-HTTLPR) gene-environment interaction (G X E) in the development of excessive alcohol intake. Few studies in humans have been conducted on this topic, yielding inconsistent results. The present study aims to further explore G x E between 5-HTTLPR and exposure to psychosocial adversity on alcohol consumption in a high-risk community sample of young adults. Methods: Data were collected as part of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study following the outcome of early risk factors from birth into young adulthood. At age 19 years, 309 participants (142 male participants, 167 female participants) were genotyped for the biallelic and triallelic 5-HTTLPR and were administered a 45-day alcohol timeline follow-back interview, providing measures of the total number of drinks and the number of binge drinking days. Psychosocial adversity was assessed at birth (family adversity) and at age 19 (negative life events). Results: In contrast to various previous reports, a significant G x E emerged, indicating that, when exposed to high psychosocial adversity, individuals with the LL genotype of 5-HTTLPR exhibited more hazardous drinking than those carrying the S allele or those without exposure to adversity. This effect, which was confined to male participants, held both for different classifications of 5-HTTLPR and different types of adversity. Conclusions: One explanation for the discrepant results might be heterogeneity in alcohol phenotypes. While the L allele relates more strongly to early-onset alcoholism, the S allele may be linked more closely to alcohol use associated with anxiety and depression.
Y1  - 2009
UR  - http://www.sciencedirect.com/science/journal/00063223
U6  - https://doi.org/10.1016/j.biopsych.2009.02.010
SN  - 0006-3223
ER  - 
TY  - JOUR
A1  - Laucht, Manfred
A1  - Treutlein, Jens
A1  - Blomeyer, Dorothea
A1  - Buchmann, Arlette F.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Jennen-Steinmetz, Christine
A1  - Rietschel, Marcella
A1  - Banaschewski, Tobias
T1  - Interactive effects of corticotropin-releasing hormone receptor 1 gene and childhood adversity on depressive symptoms in young adults findings from a longitudinal study
JF  - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
N2  - Accumulating research suggests a moderating role for the corticotropin-releasing hormone receptor 1 gene (CRHR1) in the association between childhood adversity and adult depression. The present study aims to replicate recent findings using different genetic variants and measures of early adversity assessed both prospectively and retrospectively. Data were collected in the context of an ongoing epidemiological cohort study following the outcome of early risk factors from birth into adulthood. 300 participants (137 males, 163 females) were genotyped for four CRHR1 SNPs (rs7209436, rs110402, rs242924, and rs17689882) and completed the Beck Depression Inventory at ages 19, 22 and 23 years. Childhood adversity was assessed using the Childhood Trauma Questionnaire and by a standardized parent interview yielding an index of family adversity. Our results indicate that CRHR1 and childhood adversity interacted to predict depressive symptoms in young adults. Specifically, we found that the impact of childhood maltreatment on adult depressive symptoms was significantly higher in individuals (i) with two copies of the CRHR1 TAT haplotype, and (ii) homozygous for the G allele of rs17689882. The interaction was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report, but not to prospectively ascertain objective family adversity. The present study partially replicates recent findings of a CRHR1 by childhood adversity interaction with regard to adult depression highlighting the subjective characteristics of the environmental pathogen that is operative in this interaction.
KW  - Corticotropin-releasing hormone receptor 1 gene
KW  - Depression
KW  - Maltreatment
KW  - Family adversity
KW  - Young adults
KW  - Gene-environment interaction
Y1  - 2013
U6  - https://doi.org/10.1016/j.euroneuro.2012.06.002
SN  - 0924-977X
VL  - 23
IS  - 5
SP  - 358
EP  - 367
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Laucht, Manfred
A1  - Treutlein, Jens
A1  - Blomeyer, Dorothea
A1  - Buchmann, Arlette F.
A1  - Schmidt, Martin
A1  - Esser, Günter
A1  - Jennen-Steinmetz, Christine
A1  - Reitschelb, Marcel
A1  - Banaschewski, Tobias
T1  - Interactive effects of corticotropin-releasing hormone receptor 1 gene and childhood adversity on depressive symptoms in young adults: Findings from a longitudinal study
Y1  - 2012
ER  - 
TY  - JOUR
A1  - Laucht, Manfred
A1  - Treutlein, Jens
A1  - Blomeyer, Dorothea
A1  - Buchmann, Arlette F.
A1  - Schmid, Brigitte
A1  - Becker, Katja
A1  - Zimmermann, Ulrich S.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Rietschel, Marcella
A1  - Banaschewski, Tobias
T1  - Interaction between the 5-HTTLPR serotonin transporter polymorphism and environmental adversity for mood and anxiety psychopathology : evidence from a high-risk community sample of young adults
N2  - Previous research examining gene-environment interaction (G x E) with regard to vulnerability to depression and anxiety has yielded conflicting results. The present study was designed to further investigate G x F between 5-HTTLPR and exposure to environmental adversity, using different phenotypic and genotypic characterizations as well as different types of adversity within a prospective study design. Data were available from an ongoing epidemiological cohort Study following the outcome of early risk factors from birth to adulthood. At age 19 yr, 309 participants (142 males, 167 females) were characterized on measures of depression and anxiety through interview and questionnaire (DSM-IV diagnosis, Beck Depression Inventory, Harm Avoidance). Environmental adversity was assessed at birth (family adversity), and at age 19 yr (stressful life events). Bi- and tri-allelic 5-HTTLPR genotypes were obtained from genomic DNA. Results indicated that depression and anxiety in 19-yr-olds were strongly associated with both family adversity and stressful life events. Individuals with the LL genotype of 5-HTTLPR who were exposed to high family adversity displayed significantly higher rates of depressive or anxiety disorders and had more depressive symptoms than those without either condition. This G x E replicates recent findings from an epidemiological cohort study of adolescents but is in contrast to many previous reports suggesting an interaction with the S allele. No evidence for G x E was obtained with regard to current stressful life events and trait anxiety. One possible source for the conflicting findings might be attributed to heterogeneity in depression phenotypes and environmental adversity.
Y1  - 2009
UR  - http://journals.cambridge.org/jid_PNP
U6  - https://doi.org/10.1017/S1461145708009875
SN  - 1461-1457
ER  - 
TY  - JOUR
A1  - Laucht, Manfred
A1  - Blomeyer, Dorothea
A1  - Buchmann, Arlette F.
A1  - Treutlein, Jens
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Jennen-Steinmetz, Christine
A1  - Rietschel, Marcella
A1  - Zimmermann, Ulrich S.
A1  - Banaschewski, Tobias
T1  - Catechol-O-methyltransferase Val158Met genotype, parenting practices and adolescent alcohol use: testing the differential susceptibility hypothesis
JF  - The journal of child psychology and psychiatry
N2  - Background: Recently, first evidence has been reported for a geneparenting interaction (G x E) with regard to adolescent alcohol use. The present investigation set out to extend this research using the catechol-O-methyltransferase (COMT) Val158Met polymorphism as a genetic susceptibility factor. Moreover, the current study examined whether a potential G x E would be consistent with one of two models of geneenvironment interplay (genetic vulnerability vs. differential susceptibility). Methods: Data were collected as part of an ongoing epidemiological cohort study following the outcome of early risk factors from birth into adulthood. Two hundred and eighty-five participants (130 males, 155 females) were genotyped for the COMT Val(158) Met polymorphism and were administered an alcohol interview, providing measures of current frequency and amount of drinking at ages 15 and 19 years. Information on three dimensions of perceived parenting behavior was obtained from the 15-year-olds. Results: Adolescents homozygous for the Met allele showed higher drinking activity at age 19 years when their parents had engaged in less supervision or were less involved, while their drinking activity was reduced under conditions of favorable parenting. No such relationship was found in individuals carrying the Val allele. Conclusions: The present findings correspond with the pattern of results predicted by the differential susceptibility hypothesis, suggesting that environmental variation would have a greater impact in individuals carrying a genetic susceptibility such that, in this group, exposure to negative environmental conditions would result in more adverse outcomes and the experience of favorable conditions would lead to more positive outcomes.
KW  - Catechol-O-methyltransferase gene
KW  - alcohol use
KW  - adolescents
KW  - parenting
KW  - gene-environment interaction
Y1  - 2012
U6  - https://doi.org/10.1111/j.1469-7610.2011.02408.x
SN  - 0021-9630
VL  - 53
IS  - 4
SP  - 351
EP  - 359
PB  - Wiley-Blackwell
CY  - Malden
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  - JOUR
A1  - Hohmann, Sarah
A1  - Hohm, Erika
A1  - Treutlein, Jens
A1  - Blomeyer, Dorothea
A1  - Jennen-Steinmetz, Christine
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Association of norepinephrine transporter (NET, SLC6A2) genotype with ADHD-related phenotypes: Findings of a longitudinal study from birth to adolescence
JF  - Psychiatry research : the official publication of the International Society for Neuroimaging in Psychiatry
N2  - Variation in the gene encoding for the norepinephrine transporter (NET, SLC6A2) has repeatedly been linked with ADHD, although there is some inconsistency regarding the association with specific genes. The variants for which most consistent association has been found are the NET variants rs3785157 and rs28386840. Here, we tested for their association with ADHD diagnosis and ADHD-related phenotypes during development in a longitudinal German community sample. Children were followed from age 4 to age 15, using diagnostic interviews to assess ADHD. Between the ages of 8 and 15 years, the Child Behavior Checklist (CBCL) was administered to the primary caregivers. The continuous performance task (CPT) was performed at age 15. Controlling for possible confounders, we found that homozygous carriers of the major A allele of the functional promoter variant rs28386840 displayed a higher rate of ADHD lifetime diagnosis. Moreover, homozygous carriers of the minor T allele of rs3785157 were more likely to develop ADHD and showed higher scores on the CBCL externalizing behavior scales. Additionally, we found that individuals heterozygous for rs3785157 made fewer omission errors in the CPT than homozygotes. This is the first longitudinal study to report associations between specific NET variants and ADHD-related phenotypes during the course of development. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
KW  - Attention-deficit/hyperactivity disorder
KW  - Norepinephrine transporter
KW  - Genetic association
KW  - Polymorphism
KW  - Molecular heterosis
KW  - Continuous performance task
Y1  - 2015
U6  - https://doi.org/10.1016/j.psychres.2014.12.029
SN  - 0165-1781
VL  - 226
IS  - 2-3
SP  - 425
EP  - 433
PB  - Elsevier
CY  - Clare
ER  -