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  - 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  - 
TY  - JOUR
A1  - Schmid, Brigitte
A1  - Hohm, Erika
A1  - Blomeyer, Dorothea
A1  - Zimmermann, Ulrich S.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Laucht, Manfred
T1  - Concurrent alcohol and tobacco use during early adolescence characterizes a group at risk
N2  - Aims: To investigate whether concurrent alcohol and tobacco use during early adolescence characterizes a subgroup that differs from users of one substance only regarding several risk factors for later substance use problems. Methods: Participants were from a prospective longitudinal cohort study of 384 children at risk for later psychopathology, with the majority being born with obstetric complications and psychosocial adversities. Assessments of adolescent drug consumption and related intrapersonal characteristics were obtained at age 15. Results: Compared to consumers of alcohol only, 15-year-olds drinking and smoking during the same time period (past 4 weeks) had significantly higher levels of consumption and more excessive use of alcohol, started drinking at an earlier age, had higher scores on the Fagerstrom Test for Nicotine Dependence, and more cannabis use. This group could be distinguished from users of alcohol only by higher novelty seeking and more positive alcohol effect expectancies. Compared to consumers of tobacco only, concurrent users reported higher nicotine dependence and more cannabis use. No significant differences were observed regarding frequency and age at initiation of tobacco use, tobacco-related sensitivity, self- efficacy and instrumentality as well as novelty seeking. Conclusions: Concurrent alcohol and tobacco use during early adolescence is associated with characteristics that are well known as risk factors for later alcohol use problems and dependence and that should be targeted by prevention programs.
Y1  - 2007
UR  - http://alcalc.oxfordjournals.org/
U6  - https://doi.org/10.1093/alcalc/agm024
SN  - 0735-0414
ER  - 
TY  - JOUR
A1  - Buchmann, Arlette F.
A1  - Schmid, Brigitte
A1  - Blomeyer, Dorothea
A1  - Zimmermann, Ulrich S.
A1  - Jennen-Steinmetz, Christine
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Mann, Karl F.
A1  - Laucht, Manfred
T1  - Drinking against unpleasant emotions : possible outcome of early onset of alcohol use?
N2  - Background: Recent animal and human studies indicate that the exposure to alcohol during early adolescence increases the risk for heavy alcohol use in response to stress. The purpose of this study was to examine whether this effect may be the consequence of a higher susceptibility to develop "drinking to cope" motives among early initiators. Methods: Data from 320 participants were collected as part of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study. Structured interviews at age 15 and 19 were used to assess age at first alcohol experience and drunkenness. The young adults completed questionnaires to obtain information about the occurrence of stressful life events during the past 4 years and current drinking habits. In addition, alcohol use under conditions of negative states was assessed with the Inventory of Drinking Situations. Results: The probability of young adults' alcohol use in situations characterized by unpleasant emotions was significantly increased the earlier they had initiated the use of alcohol, even when controlling for current drinking habits and stressful life events. Similar results were obtained for the age at first drunkenness. Conclusions: The findings strengthen the hypothesis that alcohol experiences during early adolescence facilitate drinking to regulate negative affect as an adverse coping strategy which may represent the starting point of a vicious circle comprising drinking to relieve stress and increased stress as a consequence of drinking.
Y1  - 2010
UR  - http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1530-0277
U6  - https://doi.org/10.1111/j.1530-0277.2010.01180.x
SN  - 0145-6008
ER  - 
TY  - JOUR
A1  - Obst, Elisabeth
A1  - Schad, Daniel
A1  - Huys, Quentin J. M.
A1  - Sebold, Miriam Hannah
A1  - Nebe, Stephan
A1  - Sommer, Christian
A1  - Smolka, Michael N.
A1  - Zimmermann, Ulrich S.
T1  - Drunk decisions
BT  - Alcohol shifts choice from habitual towards goal-directed control in adolescent intermediate-risk drinkers
JF  - Journal of Psychopharmacology
N2  - Background: Studies in humans and animals suggest a shift from goal-directed to habitual decision-making in addiction. We therefore tested whether acute alcohol administration reduces goal-directed and promotes habitual decision-making, and whether these effects are moderated by self-reported drinking problems. Methods: Fifty-three socially drinking males completed the two-step task in a randomised crossover design while receiving an intravenous infusion of ethanol (blood alcohol level=80 mg%), or placebo. To minimise potential bias by long-standing heavy drinking and subsequent neuropsychological impairment, we tested 18- to 19-year-old adolescents. Results: Alcohol administration consistently reduced habitual, model-free decisions, while its effects on goal-directed, model-based behaviour varied as a function of drinking problems measured with the Alcohol Use Disorders Identification Test. While adolescents with low risk for drinking problems (scoring <8) exhibited an alcohol-induced numerical reduction in goal-directed choices, intermediate-risk drinkers showed a shift away from habitual towards goal-directed decision-making, such that alcohol possibly even improved their performance. Conclusions: We assume that alcohol disrupted basic cognitive functions underlying habitual and goal-directed decisions in low-risk drinkers, thereby enhancing hasty choices. Further, we speculate that intermediate-risk drinkers benefited from alcohol as a negative reinforcer that reduced unpleasant emotional states, possibly displaying a novel risk factor for drinking in adolescence.
KW  - Computer-assisted Alcohol Infusion System
KW  - habitual learning
KW  - model-free and model-based decision-making
KW  - two-stage Markov decision task
KW  - subjective response to ethanol
KW  - drinking problems
KW  - real-life drinking behaviour
Y1  - 2018
U6  - https://doi.org/10.1177/0269881118772454
SN  - 0269-8811
SN  - 1461-7285
VL  - 32
IS  - 8
SP  - 855
EP  - 866
PB  - Sage Publ.
CY  - London
ER  - 
TY  - JOUR
A1  - Friedel, Eva
A1  - Sebold, Miriam Hannah
A1  - Kuitunen-Paul, Sören
A1  - Nebe, Stephan
A1  - Veer, Ilya M.
A1  - Zimmermann, Ulrich S.
A1  - Schlagenhauf, Florian
A1  - Smolka, Michael N.
A1  - Rapp, Michael Armin
A1  - Walter, Henrik
A1  - Heinz, Andreas
T1  - How Accumulated Real Life Stress Experience and Cognitive Speed Interact on Decision-Making Processes
JF  - Frontiers in human neuroscienc
N2  - Rationale: Advances in neurocomputational modeling suggest that valuation systems for goal-directed (deliberative) on one side, and habitual (automatic) decision-making on the other side may rely on distinct computational strategies for reinforcement learning, namely model-free vs. model-based learning. As a key theoretical difference, the model-based system strongly demands cognitive functions to plan actions prospectively based on an internal cognitive model of the environment, whereas valuation in the model-free system relies on rather simple learning rules from operant conditioning to retrospectively associate actions with their outcomes and is thus cognitively less demanding. Acute stress reactivity is known to impair model-based but not model-free choice behavior, with higher working memory capacity protecting the model-based system from acute stress. However, it is not clear which impact accumulated real life stress has on model-free and model-based decision systems and how this influence interacts with cognitive abilities. Methods: We used a sequential decision-making task distinguishing relative contributions of both learning strategies to choice behavior, the Social Readjustment Rating Scale questionnaire to assess accumulated real life stress, and the Digit Symbol Substitution Test to test cognitive speed in 95 healthy subjects. Results: Individuals reporting high stress exposure who had low cognitive speed showed reduced model-based but increased model-free behavioral control. In contrast, subjects exposed to accumulated real life stress with high cognitive speed displayed increased model-based performance but reduced model-free control. Conclusion: These findings suggest that accumulated real life stress exposure can enhance reliance on cognitive speed for model-based computations, which may ultimately protect the model-based system from the detrimental influences of accumulated real life stress. The combination of accumulated real life stress exposure and slower information processing capacities, however, might favor model-free strategies. Thus, the valence and preference of either system strongly depends on stressful experiences and individual cognitive capacities.
KW  - chronic stress
KW  - model-based learning
KW  - model-free learning
KW  - decision making
KW  - cognitive speed
KW  - real-life events
Y1  - 2017
U6  - https://doi.org/10.3389/fnhum.2017.00302
SN  - 1662-5161
VL  - 11
SP  - 1
EP  - 9
PB  - Frontiers Research Foundation
CY  - Lausanne
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  - Buchmann, Arlette F.
A1  - Kopf, Daniel
A1  - Westphal, Sabine
A1  - Lederbogen, Florian
A1  - Banaschewski, Tobias
A1  - Esser, Günter
A1  - Schmidt, Martin H.
A1  - Zimmermann, Ulrich S.
A1  - Laucht, Manfred
A1  - Deuschle, Michael
T1  - Impact of early parental child-rearing behavior on young adults' cardiometabolic risk profile : a prospective study
N2  - Objective: To examine prospectively whether early parental child-rearing behavior is a predictor of cardiometabolic outcome in young adulthood when other potential risk factors are controlled. Metabolic factors associated with increased risk for cardiovascular disease have been found to vary, depending on lifestyle as well as genetic predisposition. Moreover, there is evidence suggesting that environmental conditions, such as stress in pre- and postnatal life, may have a sustained impact on an individual's metabolic risk profile. Methods: Participants were drawn from a prospective, epidemiological, cohort study followed up from birth into young adulthood. Parent interviews and behavioral observations at the age of 3 months were conducted to assess child-rearing practices and mother-infant interaction in the home setting and in the laboratory. In 279 participants, anthropometric characteristics, low-density lipoprotein and high-density lipoprotein cholesterol, apolipoproteins, and triglycerides were recorded at age 19 years. In addition, structured interviews were administered to the young adults to assess indicators of current lifestyle and education. Results: Adverse early-life interaction experiences were significantly associated with lower levels of high- density lipoprotein cholesterol and apolipoprotein A1 in young adulthood. Current lifestyle variables and level of education did not account for this effect, although habitual smoking and alcohol consumption also contributed significantly to cardiometabolic outcomes. Conclusions: These findings suggest that early parental child-rearing behavior may predict health outcome in later life through its impact on metabolic parameters in adulthood.
Y1  - 2010
UR  - http://www.psychosomaticmedicine.org/
U6  - https://doi.org/10.1097/Psy.0b013e3181c88343
SN  - 0033-3174
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  - 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  - 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  - Paslakis, Georgios
A1  - Buchmann, Arlette F.
A1  - Westphal, Sabine
A1  - Banaschewski, Tobias
A1  - Hohm, Erika
A1  - Zimmermann, Ulrich S.
A1  - Laucht, Manfred
A1  - Deuschle, Michael
T1  - Intrauterine exposure to cigarette smoke is associated with increased ghrelin concentrations in adulthood
JF  - Neuroendocrinology : international journal for basic and clinical studies on neuroendocrine relationships
N2  - Background: The appetite-stimulating hormone ghrelin is a fundamental regulator of human energy metabolism. A series of studies support the notion that long-term appetite and weight regulation may be already programmed in early life and it could be demonstrated that the intrauterine environment affects the ghrelin system of the offspring. Animal studies have also shown that intrauterine programming of orexigenic systems persists even until adolescence/adulthood. Methods: We hypothesized that plasma ghrelin concentrations in adulthood may be associated with the intrauterine exposure to cigarette smoke. We examined this hypothesis in a sample of 19-year-olds followed up since birth in the framework of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study of the long-term outcome of early risk factors. Results: As a main finding, we found that ghrelin plasma concentrations in young adults who had been exposed to cigarette smoke in utero were significantly higher than in those without prenatal smoke exposure. Moreover, individuals with intrauterine nicotine exposure showed a significantly higher prevalence of own smoking habits and lower educational status compared to those in the group without exposure. Conclusion: Smoking during pregnancy may be considered as an adverse intrauterine influence that may alter the endocrine-metabolic status of the offspring even until early adulthood.
KW  - Cigarette smoke
KW  - Depression
KW  - Energy metabolism
KW  - Epigenetics
KW  - Ghrelin
KW  - Intrauterine exposure
KW  - Nicotine
Y1  - 2014
U6  - https://doi.org/10.1159/000363325
SN  - 0028-3835
SN  - 1423-0194
VL  - 99
IS  - 2
SP  - 123
EP  - 129
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Clarke, Toni-Kim
A1  - Laucht, Manfred
A1  - Ridinger, Monika
A1  - Wodarz, Norbert
A1  - Rietschel, Marcella
A1  - Maier, Wolfgang
A1  - Lathrop, Mark
A1  - Lourdusamy, Anbarasu
A1  - Zimmermann, Ulrich S.
A1  - Desrivieres, Sylvane
A1  - Schumann, Gunter
T1  - KCNJ6 is associated with adult alcohol dependence and involved in gene x early life stress interactions in adolescent alcohol drinking
JF  - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
N2  - Alcohol abuse and dependence have proven to be complex genetic traits that are influenced by environmental factors. Primate and human studies have shown that early life stress increases the propensity for alcohol abuse in later life. The reinforcing properties of alcohol are mediated by dopaminergic signaling; however, there is little evidence to indicate how stress alters alcohol reinforcement. KCNJ6 (the gene encoding G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2)) is a brain expressed potassium channel with inhibitory effects on dopaminergic tone. The properties of GIRK2 have been shown to be enhanced by the stress peptide corticotrophin-releasing hormone. Therefore, we sought to examine the role of KCNJ6 polymorphisms in adult alcohol dependence and stress-related alcohol abuse in adolescents. We selected 11 SNPs in the promoter region of KCNJ6, which were genotyped in 1152 adult alcohol dependents and 1203 controls. One SNP, rs2836016, was found to be associated with alcohol dependence (p = 0.01, false discovery rate). We then assessed rs2836016 in an adolescent sample of 261 subjects, which were characterized for early life stress and adolescent hazardous drinking, defined using the Alcohol Use Disorders Identification Test (AUDIT), to examine gene-environment interactions. In the adolescent sample, the risk genotype of rs2836016 was significantly associated with increased AUDIT scores, but only in those individuals exposed to high levels of psychosocial stress in early life (p = 0.01). Our findings show that KCNJ6 is associated with alcohol dependence and may moderate the effect of early psychosocial stress on risky alcohol drinking in adolescents. We have identified a candidate gene for future studies investigating a possible functional link between the response to stress and alcohol reinforcement.
KW  - alcoholism
KW  - genetics
KW  - GIRK2
KW  - stress
KW  - gene x environment
KW  - KCNJ6
Y1  - 2011
U6  - https://doi.org/10.1038/npp.2010.247
SN  - 0893-133X
VL  - 36
IS  - 6
SP  - 1142
EP  - 1148
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Plener, Paul L.
A1  - Zohsel, Katrin
A1  - Hohm, Erika
A1  - Buchmann, Arlette F.
A1  - Banaschewski, T.
A1  - Zimmermann, Ulrich S.
A1  - Laucht, Manfred
T1  - Lower cortisol level in response to a psychosocial stressor in young females with self-harm
JF  - Psychoneuroendocrinology
N2  - Background: Self-harm is highly prevalent in adolescence, often serving an emotion regulation function. Social stressors such as bullying are associated with self-harm. The neurobiological background of the relationship between social stressors and self-harm needs to be further understood to inform prevention and therapy. Methods: Participants were members of an epidemiological cohort study. 130 female participants underwent the Trier Social Stress Test (TSST) at age 19. Of them, 21 reported a history of self-harm as assessed by the Youth Self Report. Psychiatric diagnoses were recorded. Results: Participants with a history of self-harm showed significantly lower blood cortisol levels throughout the TSST. Early psychosocial adversity did not significantly differ between groups with and without self-harm, with self-harming participants reporting more childhood adversities. Conclusion: These results add to the limited field of studies showing an altered HPA axis activity in females with self-harm. Future studies need to address the causal mechanisms behind this association.
KW  - Self-harm
KW  - Trier Social Stress Test
KW  - TSST
KW  - Cortisol
KW  - Nonsuicidal self-injury
Y1  - 2016
U6  - https://doi.org/10.1016/j.psyneuen.2016.11.009
SN  - 0306-4530
VL  - 76
SP  - 84
EP  - 87
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Schmid, Brigitte
A1  - Buchmann, Arlette F.
A1  - Trautmann-Villalba, Patricia
A1  - Blomeyer, Dorothea
A1  - Zimmermann, Ulrich S.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Laucht, Manfred
T1  - Maternal stimulation in infancy predicts hypothalamic-pituitary-adrenal axis reactivity in young men
JF  - Journal of neural transmission
N2  - Evidence from animal research has demonstrated the effect of early maternal care on the offspring's endocrine and behavioral stress response in adulthood. The present prospective study investigates, in humans, the long-term impact of maternal responsiveness and stimulation during early mother-child interaction on adrenocorticotropic hormone (ACTH) and cortisol response to a psychosocial laboratory stressor in adulthood. The data are from an epidemiological cohort study of the long-term outcome of early risk factors assessed at birth. At age 3 months, mothers and infants were videotaped during a 10-min standardized nursing and playing situation and evaluated by trained raters for maternal stimulation and infant and maternal responsiveness. At age 19 years, 270 participants (146 females, 124 males) completed the Trier Social Stress Test. The results indicated that less maternal stimulation during early interaction at age 3 months predicted diminished plasma ACTH and cortisol increase in response to acute psychosocial stress in male, but not female offspring. In contrast, maternal responsiveness was found to be unrelated to hypothalamic-pituitary-adrenal (HPA) reactivity. In accordance with the findings from animal research, the present study provides prospective evidence in humans of a long-term association between early maternal interaction behavior and the offspring's hormonal stress response in young adulthood, suggesting that poor maternal stimulation in early infancy may result in reduced HPA axis reactivity to an acute psychosocial stressor in males.
KW  - ACTH
KW  - Cortisol
KW  - HPA axis
KW  - Mother-infant interaction
Y1  - 2013
U6  - https://doi.org/10.1007/s00702-013-0970-8
SN  - 0300-9564
VL  - 120
IS  - 8
SP  - 1247
EP  - 1257
PB  - Springer
CY  - Wien
ER  - 
TY  - JOUR
A1  - Buchmann, Arlette F.
A1  - Holz, Nathalie
A1  - Boecker-Schlier, Regina
A1  - Blomeyer, Dorothea
A1  - Rietschel, Marcella
A1  - Witt, Stephanie H.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Zimmermann, Ulrich S.
A1  - Laucht, Manfred
T1  - Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood
JF  - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
N2  - Recent research suggests an important role of FKBP5, a glucocorticoid receptor regulating co-chaperone, in the development of stress-related diseases such as depression and anxiety disorders. The present study aimed to replicate and extend previous evidence indicating that FKBP5 polymorphisms moderate hypothalamus-pituitary-adrenal (HPA) function by examining whether FKBP5 rs1360780 genotype and different measures of childhood adversity interact to predict stress-induced cortisol secretion. At age 19 years, 195 young adults (90 males, 105 females) participating in an epidemiological cohort study completed the Trier Social Stress Test (TSST) to assess cortisol stress responsiveness and were genotyped for the FKBP5 rs1360780. Childhood adversity was assessed using the Childhood Trauma Questionnaire (CTQ) and by a standardized parent interview yielding an index of family adversity. A significant interaction between genotype and childhood adversity on cortisol response to stress was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report (CTQ), but not for prospectively ascertained objective family adversity. Severity of childhood maltreatment was significantly associated with attenuated cortisol levels among carriers of the rs1360780 CC genotype, while no such effect emerged in carriers of the T allele. These findings point towards the functional involvement of FKBP5 in long-term alterations of neuroendocrine stress regulation related to childhood maltreatment, which have been suggested to represent a premorbid risk or resilience factor in the context of stress-related disorders. (C) 2013 Elsevier B.V. and ECNR This is an open access article under the CC BY-NC-ND license.
KW  - FKBP5
KW  - Stress
KW  - HPA
KW  - Cortisol
KW  - Childhood adversity
Y1  - 2014
U6  - https://doi.org/10.1016/j.euroneuro.2013.12.001
SN  - 0924-977X
SN  - 1873-7862
VL  - 24
IS  - 6
SP  - 837
EP  - 845
PB  - Elsevier
CY  - Amsterdam
ER  -