TY  - JOUR
A1  - Blomeyer, Dorothea
A1  - Buchmann, Arlette F.
A1  - Schmid, Brigitte
A1  - Jennen-Steinmetz, Christine
A1  - Schmidt, Martin H.
A1  - Banaschewski, Tobias
A1  - Laucht, Manfred
T1  - Age at first drink moderates the impact of current stressful life events on drinking behavior in young adults
JF  - Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism
N2  - Background:
 Recent evidence from animal experiments and studies in humans suggests that early age at first drink (AFD) may lead to higher stress-induced drinking. The present study aimed to extend these findings by examining whether AFD interacted with stressful life events (SLE) and/or with daily hassles regarding the impact on drinking patterns among young adults.
 Method:
 In 306 participants of an epidemiological cohort study, AFD was assessed together with SLE during the past 3 years, daily hassles in the last month, and drinking behavior at age 22. As outcome variables, 2 variables were derived, reflecting different aspects of alcohol use: the amount of alcohol consumed in the last month and the drinking frequency, indicated by the number of drinking days in the last month.
 Results:
 Linear regression models revealed an interaction effect between the continuous measures of AFD and SLE on the amount of alcohol consumed. The earlier young adults had their first alcoholic drink and the higher the levels of SLE they were exposed to, the disproportionately more alcohol they consumed. Drinking frequency was not affected by an interaction of these variables, while daily hassles and their interaction with AFD were unrelated to drinking behavior.
 Conclusions:
 These findings highlight the importance of early age at drinking onset as a risk factor for later heavy drinking under high load of SLE. Prevention programs should aim to raise age at first contact with alcohol. Additionally, support in stressful life situations and the acquisition of effective coping strategies might prevent heavy drinking in those with earlier drinking onset.
KW  - Age at First Drink
KW  - Drinking Behavior
KW  - Longitudinal Study
KW  - Stressful Life Events
KW  - Daily Hassles
Y1  - 2011
U6  - https://doi.org/10.1111/j.1530-0277.2011.01447.x
SN  - 0145-6008
VL  - 35
IS  - 6
SP  - 1142
EP  - 1148
PB  - Wiley-Blackwell
CY  - Malden
ER  - 
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  - Nikitopoulos, Joerg
A1  - Zohsel, Katrin
A1  - Blomeyer, Dorothea
A1  - Buchmann, Arlette F.
A1  - Schmid, Brigitte
A1  - Jennen-Steinmetz, Christine
A1  - Becker, Katja
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Brandeis, Daniel
A1  - Banaschewski, Tobias
A1  - Laucht, Manfred
T1  - Are infants differentially sensitive to parenting? Early maternal care, DRD4 genotype and externalizing behavior during adolescence
JF  - Journal of psychiatric research
KW  - DRD4
KW  - Early maternal care
KW  - Externalizing behavior
KW  - Adolescence
KW  - Gene-environment interaction
Y1  - 2014
U6  - https://doi.org/10.1016/j.jpsychires.2014.08.012
SN  - 0022-3956
SN  - 1879-1379
VL  - 59
SP  - 53
EP  - 59
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Boecker-Schlier, Regina
A1  - Holz, Nathalie E.
A1  - Hohm, Erika
A1  - Zohsel, Katrin
A1  - Blomeyer, Dorothea
A1  - Buchmann, Arlette F.
A1  - Baumeister, Sarah
A1  - Wolf, Isabella
A1  - Esser, Günter
A1  - Schmidt, Martin H.
A1  - Meyer-Lindenberg, Andreas
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Association between pubertal stage at first drink and neural reward processing in early adulthood
JF  - Addiction biology
N2  - Puberty is a critical time period during human development. It is characterized by high levels of risk-taking behavior, such as increased alcohol consumption, and is accompanied by various neurobiological changes. Recent studies in animals and humans have revealed that the pubertal stage at first drink (PSFD) significantly impacts drinking behavior in adulthood. Moreover, neuronal alterations of the dopaminergic reward system have been associated with alcohol abuse or addiction. This study aimed to clarify the impact of PSFD on neuronal characteristics of reward processing linked to alcohol-related problems. One hundred sixty-eight healthy young adults from a prospective study covering 25 years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. PSFD was determined according to the age at menarche or Tanner stage of pubertal development, respectively. Alcohol-related problems in early adulthood were assessed with the Alcohol Use Disorder Identification Test (AUDIT). During reward anticipation, decreased fMRI activation of the frontal cortex and increased preparatory EEG activity (contingent negative variation) occurred with pubertal compared to postpubertal first alcohol intake. Moreover, alcohol-related problems during early adulthood were increased in pubertal compared to postpubertal beginners, which was mediated by neuronal activation of the right medial frontal gyrus. At reward delivery, increased fMRI activation of the left caudate and higher feedback-related EEG negativity were detected in pubertal compared to postpubertal beginners. Together with animal findings, these results implicate PSFD as a potential modulator of psychopathology, involving altered reward anticipation. Both PSFD timing and reward processing might thus be potential targets for early prevention and intervention.
KW  - alcohol-related problems
KW  - electroencephalography
KW  - functional magnetic resonance imaging
KW  - puberty
KW  - reward processing
Y1  - 2017
U6  - https://doi.org/10.1111/adb.12413
SN  - 1355-6215
SN  - 1369-1600
VL  - 22
SP  - 1402
EP  - 1415
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Blomeyer, Dorothea
A1  - Buchmann, Arlette F.
A1  - Lascorz, Jesus
A1  - Zimmermann, Ulrich S.
A1  - Esser, Günter
A1  - Desrivieres, Sylvane
A1  - Schmidt, Martin H.
A1  - Banaschewski, Tobias
A1  - Schumann, Gunter
A1  - Laucht, Manfred
T1  - Association of PER2 genotype and stressful life events with alcohol drinking in young adults
JF  - PLoS one
N2  - Background: Clock genes govern circadian rhythms and shape the effect of alcohol use on the physiological system. Exposure to severe negative life events is related to both heavy drinking and disturbed circadian rhythmicity. The aim of this study was 1) to extend previous findings suggesting an association of a haplotype tagging single nucleotide polymorphism of PER2 gene with drinking patterns, and 2) to examine a possible role for an interaction of this gene with life stress in hazardous drinking.
 Methods: Data were collected as part of an epidemiological cohort study on the outcome of early risk factors followed since birth. At age 19 years, 268 young adults (126 males, 142 females) were genotyped for PER2 rs56013859 and were administered a 45-day alcohol timeline follow-back interview and the Alcohol Use Disorders Identification Test (AUDIT). Life stress was assessed as the number of severe negative life events during the past four years reported in a questionnaire and validated by interview.
 Results: Individuals with the minor G allele of rs56013859 were found to be less engaged in alcohol use, drinking at only 72% of the days compared to homozygotes for the major A allele. Moreover, among regular drinkers, a gene x environment interaction emerged (p = .020). While no effects of genotype appeared under conditions of low stress, carriers of the G allele exhibited less hazardous drinking than those homozygous for the A allele when exposed to high stress.
 Conclusions: These findings may suggest a role of the circadian rhythm gene PER2 in both the drinking patterns of young adults and in moderating the impact of severe life stress on hazardous drinking in experienced alcohol users. However, in light of the likely burden of multiple tests, the nature of the measures used and the nominal evidence of interaction, replication is needed before drawing firm conclusions.
Y1  - 2013
U6  - https://doi.org/10.1371/journal.pone.0059136
SN  - 1932-6203
VL  - 8
IS  - 3
PB  - PLoS
CY  - San Fransisco
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  - Buchmann, Arlette F.
A1  - Laucht, Manfred
A1  - Schmid, Brigitte
A1  - Wiedemann, Klaus
A1  - Mann, Karl F.
A1  - Zimmermann, Ulrich S.
T1  - Cigarette craving increases after a psychosocial stress test and is related to cortisol stress response but not to dependence scores in daily smokers
N2  - Stress is known to induce cigarette craving in smokers, but the underlying mechanisms are widely unknown. We investigated how dependence severity, smoking habits and stress-induced cortisol secretion are associated with increased cigarette craving after a standardised laboratory stressor. Hundred and six healthy participants (50 men, age 18-19 years) underwent a standardised public speaking stress task. In all, 35 smoked daily (DS), 13 smoked occasionally (OS), and 58 never smoked (NS). Smoking was unrestricted until 2 h before stress onset. Plasma cortisol was measured before and up to 95 min after the stressor. All current smokers rated intensity of cigarette craving immediately before and immediately after the stressor using the Brief Questionnaire of Smoking Urges (BQSU). Cortisol levels significantly increased in response to stress in all groups. The magnitude of this stress response was significantly lower in DS compared with OS and NS but did not differ between OS and NS. Baseline BQSU scores were significantly higher in DS than OS. BQSU scores increased significantly during the stress period and were positively correlated to the cortisol response in the DS but were unrelated to their nicotine dependence scores. In OS, no change in cigarette craving could be observed. In daily smokers, cigarette craving is increased after compared with before stress exposure and is related to the magnitude of cortisol stress response rather than to severity of nicotine dependence. This result supports, but does not prove, the concept that hypothalamus-pituitary-adrenal stimulation is one of the mechanisms how stress can elicit cigarette craving.
Y1  - 2010
UR  - http://jop.sagepub.com/
U6  - https://doi.org/10.1177/0269881108095716
SN  - 0269-8811
ER  -