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  - 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  - 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  - Buchmann, Arlette F.
A1  - Hellweg, Rainer
A1  - Rietschel, Marcella
A1  - Treutlein, Jens
A1  - Witt, Stephanie H.
A1  - Zimmermann, Ulrich S.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Laucht, Manfred
A1  - Deuschle, Michael
T1  - 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
JF  - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
N2  - 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.
KW  - BDNF
KW  - 5-HTTLPR
KW  - Human
KW  - Early psychosocial adversity
KW  - Longitudinal study
KW  - Depression
Y1  - 2013
U6  - https://doi.org/10.1016/j.euroneuro.2012.09.003
SN  - 0924-977X
VL  - 23
IS  - 8
SP  - 902
EP  - 909
PB  - Elsevier
CY  - Amsterdam
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  - 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  - Buchmann, Arlette F.
A1  - Zohsel, Katrin
A1  - Blomeyer, Dorothea
A1  - Hohm, Erika
A1  - Hohmann, Sarah
A1  - Jennen-Steinmetz, Christine
A1  - Treutlein, Jens
A1  - Becker, Katja
A1  - Banaschewski, Tobias
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Brandeis, Daniel
A1  - Poustka, Luise
A1  - Zimmermann, Ulrich S.
A1  - Laucht, Manfred
T1  - Interaction between prenatal stress and dopamine D4 receptor genotype in predicting aggression and cortisol levels in young adults
JF  - Psychopharmacology
N2  - Considerable evidence suggests that genetic factors combine with environmental influences to impact on the development of aggressive behavior. A genetic variant that has repeatedly been reported to render individuals more sensitive to the presence of adverse experiences, including stress exposure during fetal life, is the seven-repeat allele of the dopamine D4 receptor (DRD4) gene.
 The present investigation concentrated on the interplay of prenatal maternal stress and DRD4 genotype in predicting self-reported aggression in young adults. As disruption of the hypothalamic-pituitary-adrenal system has been discussed as a pathophysiological pathway to aggression, cortisol stress reactivity was additionally examined.
 As part of an epidemiological cohort study, prenatal maternal stress was assessed by maternal interview 3 months after childbirth. Between the ages of 19 and 23 years, 298 offspring (140 males, 158 females) completed the Young Adult Self-Report to measure aggressive behavior and were genotyped for the DRD4 gene. At 19 years, 219 participants additionally underwent the Trier Social Stress Test to determine cortisol reactivity.
 Extending earlier findings with respect to childhood antisocial behavior, the results revealed that, under conditions of higher prenatal maternal stress, carriers of the DRD4 seven-repeat allele displayed more aggression in adulthood (p = 0.032). Moreover, the same conditions which seemed to promote aggression were found to predict attenuated cortisol secretion (p = 0.028).
 This is the first study to indicate a long-term impact of prenatal stress exposure on the cortisol stress response depending on DRD4 genotype.
KW  - Prenatal stress
KW  - Aggression
KW  - Cortisol
KW  - DRD4
KW  - Gene-environment interaction
Y1  - 2014
U6  - https://doi.org/10.1007/s00213-014-3484-7
SN  - 0033-3158
SN  - 1432-2072
VL  - 231
IS  - 16
SP  - 3089
EP  - 3097
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Buchmann, Arlette F.
A1  - Schmid, Brigitte
A1  - Blomeyer, Dorothea
A1  - Becker, Katja
A1  - Treutlein, Jens
A1  - Zimmermann, Ulrich S.
A1  - Jennen-Steinmetz, Christine
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Rietschel, Marcella
A1  - Schumann, Gunter
A1  - Laucht, Manfred
T1  - Impact of age at first drink on vulnerability to alcohol-related problems : testing the marker hypothesis in a prospective study of young adults
N2  - There is ample evidence that the early initiation of alcohol use is a risk factor for the development of later alcohol-related problems. The purpose of the current study was to examine whether this association can be explained by indicators of a common underlying susceptibility or whether age at drinking onset may be considered as an independent predictor of later drinking behavior, suggesting a potential causal relationship. Participants were drawn from a prospective cohort study of the long-term outcomes of early risk factors followed up from birth onwards. Structured interviews were administered to 304 participants to assess age at first drink and current drinking behavior. Data on risk factors, including early family adversity, parental alcohol use, childhood psychopathology and stressful life events, were repeatedly collected during childhood using standardized parent interviews. In addition, information on genotype was considered. Results confirmed previous work demonstrating that hazardous alcohol consumption is related to early-adolescent drinking onset. A younger age of first drink was significantly predicted by 5-HTTLPR genotype and the degree of preceding externalizing symptoms, and both factors were related to increased consumption or harmful alcohol use at age 19. However, even after controlling for these potential explanatory factors, earlier age at drinking onset remained a strong predictor of heavy alcohol consumption in young adulthood. The present longitudinal study adds to the current literature indicating that the early onset - adult hazardous drinking association cannot solely be attributed to shared genetic and psychopathologic risk factors as examined in this study.
Y1  - 2009
UR  - http://www.sciencedirect.com/science/journal/00223956
U6  - https://doi.org/10.1016/j.jpsychires.2009.02.006
SN  - 0022-3956
ER  -