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  - 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  - 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  - GEN
A1  - Laucht, Manfred
A1  - Blomeyer, Dorothea
A1  - Buchmann, Arlette F.
A1  - Treutlein, Jens
A1  - Shmidt, 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
Y1  - 2012
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  - Bender, Stephan
A1  - Rellum, Thomas
A1  - Freitag, Christine
A1  - Resch, Franz
A1  - Rietschel, Marcella
A1  - Treutlein, Jens
A1  - Jennen-Steinmetz, Christine
A1  - Brandeis, Daniel
A1  - Banaschewski, Tobias
A1  - Laucht, Manfred
T1  - Dopamine inactivation efficacy related to functional DAT1 and COMT variants influences motor response evaluation
JF  - PLoS one
N2  - Background: Dopamine plays an important role in orienting, response anticipation and movement evaluation. Thus, we examined the influence of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of motor processing in a contingent negative variation (CNV) task.
 Methods: 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as motor postimperative negative variation were assessed. Adolescents were genotyped for the COMT Val(158) Met and two DAT1 polymorphisms (variable number tandem repeats in the 3'-untranslated region and in intron 8).
 Results: The results revealed a significant interaction between COMT and DAT1, indicating that COMT exerted stronger effects on lateralized motor post-processing (centro-parietal motor postimperative negative variation) in homozygous carriers of a DAT1 haplotype increasing DAT1 expression. Source analysis showed that the time interval 500-1000 ms after the motor response was specifically affected in contrast to preceding movement anticipation and programming stages, which were not altered.
 Conclusions: Motor slow negative waves allow the genomic imaging of dopamine inactivation effects on cortical motor post-processing during response evaluation. This is the first report to point towards epistatic effects in the motor system during response evaluation, i.e. during the post-processing of an already executed movement rather than during movement programming.
Y1  - 2012
U6  - https://doi.org/10.1371/journal.pone.0037814
SN  - 1932-6203
VL  - 7
IS  - 5
PB  - PLoS
CY  - San Fransisco
ER  - 
TY  - JOUR
A1  - Laucht, Manfred
A1  - Skowronek, Markus H.
A1  - Becker, Katja
A1  - Schulze, Thomas G.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Rietschel, Marcella
T1  - Environmental risk factors and attention-deficit : hyperactivity discorder symptoms ; reply
Y1  - 2008
SN  - 0003-990X
ER  - 
TY  - JOUR
A1  - Holz, Nathalie
A1  - Boecker-Schlier, Regina
A1  - Buchmann, Arlette F.
A1  - Blomeyer, Dorothea
A1  - Baumeister, Sarah
A1  - Hohmann, Sarah
A1  - Jennen-Steinmetz, Christine
A1  - Wolf, Isabella
A1  - Rietschel, Marcella
A1  - Witt, Stephanie H.
A1  - Plichta, Michael M.
A1  - Meyer-Lindenberg, Andreas
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Evidence for a Sex-Dependent MAOAx Childhood Stress Interaction in the Neural Circuitry of Aggression
JF  - Cerebral cortex
N2  - Converging evidence emphasizes the role of an interaction between monoamine oxidase A (MAOA) genotype, environmental adversity, and sex in the pathophysiology of aggression. The present study aimed to clarify the impact of this interaction on neural activity in aggression-related brain systems. Functional magnetic resonance imaging was performed in 125 healthy adults from a high-risk community sample followed since birth. DNA was genotyped for the MAOA-VNTR (variable number of tandem repeats). Exposure to childhood life stress (CLS) between the ages of 4 and 11 years was assessed using a standardized parent interview, aggression by the Youth/Young Adult Self-Report between the ages of 15 and 25 years, and the VIRA-R (Vragenlijst Instrumentele En Reactieve Agressie) at the age of 15 years. Significant interactions were obtained between MAOA genotype, CLS, and sex relating to amygdala, hippocampus, and anterior cingulate cortex (ACC) response, respectively. Activity in the amygdala and hippocampus during emotional face-matching increased with the level of CLS in male MAOA-L, while decreasing in male MAOA-H, with the reverse pattern present in females. Findings in the opposite direction in the ACC during a flanker NoGo task suggested that increased emotional activity coincided with decreased inhibitory control. Moreover, increasing amygdala activity was associated with higher Y(A)SR aggression in male MAOA-L and female MAOA-H carriers. Likewise, a significant association between amygdala activity and reactive aggression was detected in female MAOA-H carriers. The results point to a moderating role of sex in the MAOAx CLS interaction for intermediate phenotypes of emotional and inhibitory processing, suggesting a possible mechanism in conferring susceptibility to violence-related disorders.
KW  - aggression
KW  - amygdala
KW  - fMRI
KW  - life stress
KW  - MAOA
Y1  - 2016
U6  - https://doi.org/10.1093/cercor/bhu249
SN  - 1047-3211
SN  - 1460-2199
VL  - 26
SP  - 904
EP  - 914
PB  - Oxford Univ. Press
CY  - Cary
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  - 
TY  - JOUR
A1  - Wolf, Isabell Ann-Cathrin
A1  - Gilles, Maria
A1  - Peus, Verena
A1  - Scharnholz, Barbara
A1  - Seibert, Julia
A1  - Jennen-Steinmetz, Christine
A1  - Krumm, Bertram
A1  - Rietschel, Marcella
A1  - Deuschle, Michael
A1  - Laucht, Manfred
T1  - Impact of prenatal stress on mother-infant dyadic behavior during the still-face paradigm
JF  - 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)
N2  - 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.
KW  - Prenatal stress
KW  - Face-to-face still-face paradigm
KW  - Resilience
KW  - Psychosocial stress
KW  - Cortisol
Y1  - 2018
U6  - https://doi.org/10.1186/s40479-018-0078-8
SN  - 2051-6673
VL  - 5
PB  - BioMed Central
CY  - London
ER  -