@misc{GarbusowSommerNebeetal.2018, author = {Garbusow, Maria and Sommer, Christian and Nebe, Stephan and Sebold, Miriam Hannah and Kuitunen-Paul, S{\"o}ren and Wittchen, Hans-Ulrich and Smolka, Michael N. and Zimmermann, Ulrich S. and Rapp, Michael Armin and Huys, Quentin J. M. and Schlagenhauf, Florian and Heinz, Andreas}, title = {Multi-level evidence of general pavlovian-to-instrumental transfer in alcohol use disorder}, series = {Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism}, volume = {42}, journal = {Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism}, publisher = {Wiley}, address = {Hoboken}, issn = {0145-6008}, pages = {128A -- 128A}, year = {2018}, language = {en} } @article{SekutowiczGuggenmosKuitunenPauletal.2019, author = {Sekutowicz, Maria and Guggenmos, Matthias and Kuitunen-Paul, S{\"o}ren and Garbusow, Maria and Sebold, Miriam Hannah and Pelz, Patricia and Priller, Josef and Wittchen, Hans-Ulrich and Smolka, Michael N. and Zimmermann, Ulrich S. and Heinz, Andreas and Sterzer, Philipp and Schmack, Katharina}, title = {Neural Response Patterns During Pavlovian-to-Instrumental Transfer Predict Alcohol Relapse and Young Adult Drinking}, series = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry}, volume = {86}, journal = {Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry}, number = {11}, publisher = {Elsevier}, address = {New York}, issn = {0006-3223}, doi = {10.1016/j.biopsych.2019.06.028}, pages = {857 -- 863}, year = {2019}, abstract = {BACKGROUND: Pavlovian-to-instrumental transfer (PIT) describes the influence of conditioned stimuli on instrumental behaviors and is discussed as a key process underlying substance abuse. Here, we tested whether neural responses during alcohol-related PIT predict future relapse in alcohol-dependent patients and future drinking behavior in adolescents. METHODS: Recently detoxified alcohol-dependent patients (n = 52) and young adults without dependence (n = 136) underwent functional magnetic resonance imaging during an alcohol-related PIT paradigm, and their drinking behavior was assessed in a 12-month follow-up. To predict future drinking behavior from PIT activation patterns, we used a multivoxel classification scheme based on linear support vector machines. RESULTS: When training and testing the classification scheme in patients, PIT activation patterns predicted future relapse with 71.2\% accuracy. Feature selection revealed that classification was exclusively based on activation patterns in medial prefrontal cortex. To probe the generalizability of this functional magnetic resonance imaging-based prediction of future drinking behavior, we applied the support vector machine classifier that had been trained on patients to PIT functional magnetic resonance imaging data from adolescents. An analysis of cross-classification predictions revealed that those young social drinkers who were classified as abstainers showed a greater reduction in alcohol consumption at 12-month follow-up than those classified as relapsers (Delta = -24.4 +/- 6.0 g vs. -5.7 +/- 3.6 g; p = .019). CONCLUSIONS: These results suggest that neural responses during PIT could constitute a generalized prognostic marker for future drinking behavior in established alcohol use disorder and in at-risk states.}, language = {en} } @article{SchadGarbusowFriedeletal.2018, author = {Schad, Daniel and Garbusow, Maria and Friedel, Eva and Sommer, Christian and Sebold, Miriam Hannah and H{\"a}gele, Claudia and Bernhardt, Nadine and Nebe, Stephan and Kuitunen-Paul, S{\"o}ren and Liu, Shuyan and Eichmann, Uta and Beck, Anne and Wittchen, Hans-Ulrich and Walter, Henrik and Sterzer, Philipp and Zimmermann, Ulrich S. and Smolka, Michael N. and Schlagenhauf, Florian and Huys, Quentin J. M. and Heinz, Andreas and Rapp, Michael Armin}, title = {Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk}, series = {European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry}, volume = {269}, journal = {European archives of psychiatry and clinical neuroscience : official organ of the German Society for Biological Psychiatry}, number = {3}, publisher = {Springer}, address = {Heidelberg}, issn = {0940-1334}, doi = {10.1007/s00406-017-0860-4}, pages = {295 -- 308}, year = {2018}, abstract = {The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.}, language = {en} } @article{GarbusowSchadSeboldetal.2016, author = {Garbusow, Maria and Schad, Daniel and Sebold, Miriam Hannah and Friedel, Eva and Bernhardt, Nadine and Koch, Stefan P. and Steinacher, Bruno and Kathmann, Norbert and Geurts, Dirk E. M. and Sommer, Christian and Mueller, Dirk K. and Nebe, Stephan and Paul, Soeren and Wittchen, Hans-Ulrich and Zimmermann, Ulrich S. and Walter, Henrik and Smolka, Michael N. and Sterzer, Philipp and Rapp, Michael Armin and Huys, Quentin J. M. and Schlagenhauf, Florian and Heinz, Andreas}, title = {Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence}, series = {Addiction biology}, volume = {21}, journal = {Addiction biology}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1355-6215}, doi = {10.1111/adb.12243}, pages = {719 -- 731}, year = {2016}, abstract = {In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.}, language = {en} } @article{SommerGarbusowJuengeretal.2017, author = {Sommer, C. and Garbusow, Maria and Juenger, E. and Pooseh, S. and Bernhardt, Nadine and Birkenstock, J. and Schad, Daniel and Jabs, B. and Gloeckler, T. and Huys, Quentin J. M. and Heinz, A. and Smolka, Michael N. and Zimmermann, Ulrich S.}, title = {Strong seduction: impulsivity and the impact of contextual cues on instrumental behavior in alcohol dependence}, series = {Translational Psychiatry}, volume = {7}, journal = {Translational Psychiatry}, publisher = {Nature Publ. Group}, address = {New York}, issn = {2158-3188}, doi = {10.1038/tp.2017.158}, pages = {1209 -- 1222}, year = {2017}, abstract = {Alcohol-related cues acquire incentive salience through Pavlovian conditioning and then can markedly affect instrumental behavior of alcohol-dependent patients to promote relapse. However, it is unclear whether similar effects occur with alcohol-unrelated cues. We tested 116 early-abstinent alcohol-dependent patients and 91 healthy controls who completed a delay discounting task to assess choice impulsivity, and a Pavlovian-to-instrumental transfer (PIT) paradigm employing both alcohol-unrelated and alcohol-related stimuli. To modify instrumental choice behavior, we tiled the background of the computer screen either with conditioned stimuli (CS) previously generated by pairing abstract pictures with pictures indicating monetary gains or losses, or with pictures displaying alcohol or water beverages. CS paired to money gains and losses affected instrumental choices differently. This PIT effect was significantly more pronounced in patients compared to controls, and the group difference was mainly driven by highly impulsive patients. The PIT effect was particularly strong in trials in which the instrumental stimulus required inhibition of instrumental response behavior and the background CS was associated to monetary gains. Under that condition, patients performed inappropriate approach behavior, contrary to their previously formed behavioral intention. Surprisingly, the effect of alcohol and water pictures as background stimuli resembled that of aversive and appetitive CS, respectively. These findings suggest that positively valenced background CS can provoke dysfunctional instrumental approach behavior in impulsive alcohol-dependent patients. Consequently, in real life they might be easily seduced by environmental cues to engage in actions thwarting their long-term goals. Such behaviors may include, but are not limited to, approaching alcohol.}, language = {en} } @article{PlenerZohselHohmetal.2017, author = {Plener, Paul L. and Zohsel, Katrin and Hohm, Erika and Buchmann, Arlette F. and Banaschewski, T. and Zimmermann, Ulrich S. and Laucht, Manfred}, title = {Lower cortisol level in response to a psychosocial stressor in young females with self-harm}, series = {Psychoneuroendocrinology}, volume = {76}, journal = {Psychoneuroendocrinology}, publisher = {Elsevier}, address = {Oxford}, issn = {0306-4530}, doi = {10.1016/j.psyneuen.2016.11.009}, pages = {84 -- 87}, year = {2017}, abstract = {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.}, language = {en} } @article{LauchtTreutleinBlomeyeretal.2009, author = {Laucht, Manfred and Treutlein, Jens and Blomeyer, Dorothea and Buchmann, Arlette F. and Schmid, Brigitte and Becker, Katja and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Rietschel, Marcella and Banaschewski, Tobias}, title = {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}, issn = {1461-1457}, doi = {10.1017/S1461145708009875}, year = {2009}, abstract = {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.}, language = {en} } @article{LauchtTreutleinSchmidetal.2009, author = {Laucht, Manfred and Treutlein, Jens and Schmid, Brigitte and Blomeyer, Dorothea and Becker, Katja and Buchmann, Arlette F. and Schmidt, Martin H. and Esser, G{\"u}nter and Jennen-Steinmetz, Christine and Rietschel, Marcella and Zimmermann, Ulrich S. and Banaschewski, Tobias}, title = {Impact of psychosocial adversity on alcohol intake in young adults : moderation by the LL genotype of the serotonin transporter polymorphism}, issn = {0006-3223}, doi = {10.1016/j.biopsych.2009.02.010}, year = {2009}, abstract = {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.}, language = {en} } @article{SchmidHohmBlomeyeretal.2007, author = {Schmid, Brigitte and Hohm, Erika and Blomeyer, Dorothea and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Laucht, Manfred}, title = {Concurrent alcohol and tobacco use during early adolescence characterizes a group at risk}, issn = {0735-0414}, doi = {10.1093/alcalc/agm024}, year = {2007}, abstract = {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.}, language = {en} } @article{SchmidBlomeyerBeckeretal.2009, author = {Schmid, Brigitte and Blomeyer, Dorothea and Becker, Katja and Treutlein, Jens and Zimmermann, Ulrich S. and Buchmann, Arlette F. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Rietschel, Marcella and Laucht, Manfred}, title = {The interaction between the dopamine transporter gene and age at onset in relation to tobacco and alcohol use among 19-year-olds}, issn = {1355-6215}, doi = {10.1111/j.1369-1600.2009.00171.x}, year = {2009}, abstract = {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.}, language = {en} } @article{BuchmannKopfWestphaletal.2010, author = {Buchmann, Arlette F. and Kopf, Daniel and Westphal, Sabine and Lederbogen, Florian and Banaschewski, Tobias and Esser, G{\"u}nter and Schmidt, Martin H. and Zimmermann, Ulrich S. and Laucht, Manfred and Deuschle, Michael}, title = {Impact of early parental child-rearing behavior on young adults' cardiometabolic risk profile : a prospective study}, issn = {0033-3174}, doi = {10.1097/Psy.0b013e3181c88343}, year = {2010}, abstract = {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.}, language = {en} } @article{BuchmannLauchtSchmidetal.2010, author = {Buchmann, Arlette F. and Laucht, Manfred and Schmid, Brigitte and Wiedemann, Klaus and Mann, Karl F. and Zimmermann, Ulrich S.}, title = {Cigarette craving increases after a psychosocial stress test and is related to cortisol stress response but not to dependence scores in daily smokers}, issn = {0269-8811}, doi = {10.1177/0269881108095716}, year = {2010}, abstract = {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.}, language = {en} } @article{BuchmannSchmidBlomeyeretal.2010, author = {Buchmann, Arlette F. and Schmid, Brigitte and Blomeyer, Dorothea and Zimmermann, Ulrich S. and Jennen-Steinmetz, Christine and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Mann, Karl F. and Laucht, Manfred}, title = {Drinking against unpleasant emotions : possible outcome of early onset of alcohol use?}, issn = {0145-6008}, doi = {10.1111/j.1530-0277.2010.01180.x}, year = {2010}, abstract = {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.}, language = {en} } @article{SchmidBuchmannTrautmannVillalbaetal.2013, author = {Schmid, Brigitte and Buchmann, Arlette F. and Trautmann-Villalba, Patricia and Blomeyer, Dorothea and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred}, title = {Maternal stimulation in infancy predicts hypothalamic-pituitary-adrenal axis reactivity in young men}, series = {Journal of neural transmission}, volume = {120}, journal = {Journal of neural transmission}, number = {8}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-013-0970-8}, pages = {1247 -- 1257}, year = {2013}, abstract = {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.}, language = {en} } @article{BuchmannHellwegRietscheletal.2013, author = {Buchmann, Arlette F. and Hellweg, Rainer and Rietschel, Marcella and Treutlein, Jens and Witt, Stephanie H. and Zimmermann, Ulrich S. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred and Deuschle, Michael}, title = {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}, series = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {23}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, number = {8}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0924-977X}, doi = {10.1016/j.euroneuro.2012.09.003}, pages = {902 -- 909}, year = {2013}, abstract = {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.}, language = {en} } @misc{LauchtBlomeyerBuchmannetal.2012, author = {Laucht, Manfred and Blomeyer, Dorothea and Buchmann, Arlette F. and Treutlein, Jens and Shmidt, Martin H. and Esser, G{\"u}nter and Jennen-Steinmetz, Christine and Rietschel, Marcella and Zimmermann, Ulrich S. and Banaschewski, Tobias}, title = {Catechol-O-methyltransferase Val158Met genotype, parenting practices and adolescent alcohol use: testing the differential susceptibility hypothesis}, year = {2012}, language = {en} } @article{PaslakisBuchmannWestphaletal.2014, author = {Paslakis, Georgios and Buchmann, Arlette F. and Westphal, Sabine and Banaschewski, Tobias and Hohm, Erika and Zimmermann, Ulrich S. and Laucht, Manfred and Deuschle, Michael}, title = {Intrauterine exposure to cigarette smoke is associated with increased ghrelin concentrations in adulthood}, series = {Neuroendocrinology : international journal for basic and clinical studies on neuroendocrine relationships}, volume = {99}, journal = {Neuroendocrinology : international journal for basic and clinical studies on neuroendocrine relationships}, number = {2}, publisher = {Karger}, address = {Basel}, issn = {0028-3835}, doi = {10.1159/000363325}, pages = {123 -- 129}, year = {2014}, abstract = {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.}, language = {en} } @article{LauchtBlomeyerBuchmannetal.2012, author = {Laucht, Manfred and Blomeyer, Dorothea and Buchmann, Arlette F. and Treutlein, Jens and Schmidt, Martin H. and Esser, G{\"u}nter and Jennen-Steinmetz, Christine and Rietschel, Marcella and Zimmermann, Ulrich S. and Banaschewski, Tobias}, title = {Catechol-O-methyltransferase Val158Met genotype, parenting practices and adolescent alcohol use: testing the differential susceptibility hypothesis}, series = {The journal of child psychology and psychiatry}, volume = {53}, journal = {The journal of child psychology and psychiatry}, number = {4}, publisher = {Wiley-Blackwell}, address = {Malden}, issn = {0021-9630}, doi = {10.1111/j.1469-7610.2011.02408.x}, pages = {351 -- 359}, year = {2012}, abstract = {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.}, language = {en} } @article{WittBuchmannBlomeyeretal.2011, author = {Witt, Stephanie H. and Buchmann, Arlette F. and Blomeyer, Dorothea and Nieratschker, Vanessa and Treutlein, Jens and Esser, G{\"u}nter and Schmidt, Martin H. and Bidlingmaier, Martin and Wiedemann, Klaus and Rietschel, Marcella and Laucht, Manfred and Wuest, Stefan and Zimmermann, Ulrich S.}, title = {An interaction between a neuropeptide Y gene polymorphism and early adversity modulates endocrine stress responses}, series = {Psychoneuroendocrinology}, volume = {36}, journal = {Psychoneuroendocrinology}, number = {7}, publisher = {Elsevier}, address = {Oxford}, issn = {0306-4530}, doi = {10.1016/j.psyneuen.2010.12.015}, pages = {1010 -- 1020}, year = {2011}, abstract = {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.}, language = {en} } @article{BuchmannHolzBoeckerSchlieretal.2014, author = {Buchmann, Arlette F. and Holz, Nathalie and Boecker-Schlier, Regina and Blomeyer, Dorothea and Rietschel, Marcella and Witt, Stephanie H. and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Brandeis, Daniel and Zimmermann, Ulrich S. and Laucht, Manfred}, title = {Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood}, series = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {24}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, number = {6}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0924-977X}, doi = {10.1016/j.euroneuro.2013.12.001}, pages = {837 -- 845}, year = {2014}, abstract = {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.}, language = {en} }