@article{SendBardtkeGillesetal.2019, author = {Send, Tabea and Bardtke, S. and Gilles, M. and Wolf, I. A. C. and S{\"u}tterlin, Marc Wolf and Wudy, S. A. and Wang, R. and Laucht, Manfred and Witt, Stephanie H. and Rietschel, Marcella and Streit, Fabian and Deuschle, Michael}, title = {Prenatal maternal stress is associated with lower cortisol and cortisone levels in the first morning urine of 45-month-old children}, series = {Psychoneuroendocrinology}, volume = {103}, journal = {Psychoneuroendocrinology}, publisher = {Elsevier}, address = {Oxford}, issn = {0306-4530}, doi = {10.1016/j.psyneuen.2019.01.017}, pages = {219 -- 224}, year = {2019}, abstract = {Prenatal stress (PS) has been related to altered hypothalamic-pituitary-adrenal (HPA) axis activity later in life. So far, studies in children assessing HPA axis functioning have focused on salivary cortisol, reflecting daytime activity. The present work is part of a prospective study and aims to extend knowledge about the association between PS and HPA axis regulation in children. To do so, we investigated cortisol, cortisone, and the ratio cortisone/(cortisone + cortisol) in the first morning urine of 45-month-old children in relation to several measures of maternal stress during pregnancy. Urinary cortisol and cortisone were measured by online turbulent flow chromatography coupled with high performance liquid chromatography-tandem mass spectrometry. PS was defined as: perceived stress for aim 1 (Perceived Stress Scale; n = 280); presence of self-reported (n = 371) and expert-rated psychopathology for aim 2 (Mini International Neuropsychiatric Interview; n = 281); continuous measures of anxiety and depression for exploratory aim 3 (State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale; n = 280). The ratio cortisone/(cortisone + cortisol) as a global marker for the balance between the enzymes metabolizing cortisol to cortisone and vice versa (11 beta-hydroxysteroid dehydrogenases type 1 and 2; 11 beta-HSD1 and 2) was not associated with any measure of maternal PS (aims 1-3). The present study provides insight into possible programming effects of PS on nocturnal HPA axis activity and a proxy of 11 beta-HSD in a large sample. The results suggest that the nocturnal rate of cortisol production is lower in children exposed to PS, but do not support the hypothesis of divergent 11 beta-HSD activity.}, language = {en} } @misc{SendGillesCoddetal.2018, author = {Send, T. S. and Gilles, M. and Codd, V. and Wolf, I. A. C. and Bardtke, S. and Streit, Fabian and Strohmaier, Jana and Frank, Josef and Schendel, D. and Sutterlin, M. W. and Denniff, M. and Laucht, Manfred and Samani, N. J. and Deuschle, Michael and Rietschel, Marcella and Witt, Stephanie H.}, title = {Telomere length in newborns is related to maternal stress during pregnancy Response}, series = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {43}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, number = {11}, publisher = {Nature Publ. Group}, address = {London}, issn = {0893-133X}, doi = {10.1038/s41386-018-0079-8}, pages = {2164 -- 2164}, year = {2018}, language = {en} } @article{HolzBoeckerSchlierJennenSteinmetzetal.2018, author = {Holz, Nathalie E. and Boecker-Schlier, Regina and Jennen-Steinmetz, Christine and Hohm, Erika and Buchmann, Arlette F. and Blomeyer, Dorothea and Baumeister, Sarah and Plichta, Michael M. and Esser, G{\"u}nter and Schmidt, Martin and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Early maternal care may counteract familial liability for psychopathology in the reward circuitry}, series = {Social Cognitive and Affective Neuroscience}, volume = {13}, journal = {Social Cognitive and Affective Neuroscience}, number = {11}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1749-5016}, doi = {10.1093/scan/nsy087}, pages = {1191 -- 1201}, year = {2018}, abstract = {Reward processing is altered in various psychopathologies and has been shown to be susceptible to genetic and environmental influences. Here, we examined whether maternal care may buffer familial risk for psychiatric disorders in terms of reward processing. Functional magnetic resonance imaging during a monetary incentive delay task was acquired in participants of an epidemiological cohort study followed since birth (N = 172, 25 years). Early maternal stimulation was assessed during a standardized nursing/playing setting at the age of 3 months. Parental psychiatric disorders (familial risk) during childhood and the participants' previous psychopathology were assessed by diagnostic interview. With high familial risk, higher maternal stimulation was related to increasing activation in the caudate head, the supplementary motor area, the cingulum and the middle frontal gyrus during reward anticipation, with the opposite pattern found in individuals with no familial risk. In contrast, higher maternal stimulation was associated with decreasing caudate head activity during reward delivery and reduced levels of attention deficit hyperactivity disorder (ADHD) in the high-risk group. Decreased caudate head activity during reward anticipation and increased activity during delivery were linked to ADHD. These findings provide evidence of a long-term association of early maternal stimulation on both adult neurobiological systems of reward underlying externalizing behavior and ADHD during development.}, language = {en} } @article{WolfGillesPeusetal.2018, author = {Wolf, Isabell Ann-Cathrin and Gilles, Maria and Peus, Verena and Scharnholz, Barbara and Seibert, Julia and Jennen-Steinmetz, Christine and Krumm, Bertram and Rietschel, Marcella and Deuschle, Michael and Laucht, Manfred}, title = {Impact of prenatal stress on mother-infant dyadic behavior during the still-face paradigm}, series = {Borderline Personality Disorder and Emotion Dysregulation : the official journal of the National Education Alliance for Borderline Personality Disorder (NEA.BPD) and Dachverband Dialektisch Behaviorale Therapie (DDBT)}, volume = {5}, journal = {Borderline Personality Disorder and Emotion Dysregulation : the official journal of the National Education Alliance for Borderline Personality Disorder (NEA.BPD) and Dachverband Dialektisch Behaviorale Therapie (DDBT)}, publisher = {BioMed Central}, address = {London}, issn = {2051-6673}, doi = {10.1186/s40479-018-0078-8}, pages = {13}, year = {2018}, abstract = {Background: Mother-infant interaction provides important training for the infant's ability to cope with stress and the development of resilience. Prenatal stress (PS) and its impact on the offspring's development have long been a focus of stress research, with studies highlighting both harmful and beneficial effects. The aim of the current study was to examine the possible influence of both psychological stress and hypothalamic-pituitary-adrenal (HPA) axis activity during pregnancy with mother-child dyadic behavior following stress exposure. Methods: The behavior of 164 mother-infant dyads during the still-face situation was filmed at six months postpartum and coded into three dyadic patterns: 1) both positive, 2) infant protesting-mother positive, and 3) infant protesting-mother negative. PS exposure was assessed prenatally according to psychological measures (i.e., psychopathological, perceived and psychosocial PS; n = 164) and HPA axis activity measures (maternal salivary cortisol, i.e., cortisol decline and area under the curve with respect to ground (AUCg); n = 134). Results: Mother-infant dyads in both the high- and low-stress groups showed decreasing positive and increasing negative dyadic behavior in the reunion episode, which is associated with the well-known "still-face" and "carry-over" effect. Furthermore, mother-infant dyads with higher psychosocial PS exhibited significantly more positive dyadic behavior than the low psychosocial PS group in the first play episode, but not in the reunion episode. Similarly, mother-infant dyads with high HPA axis activity (i.e. high AUCg) but steeper diurnal cortisol decline (i.e. cortisol decline) displayed significantly less negative behavior in the reunion episode than dyads with low HPA axis activity. No significant results were found for psychopathological stress and perceived stress. Conclusions: The results suggest a beneficial effect of higher psychosocial PS and higher prenatal maternal HPA axis activity in late gestation, which is in line with "stress inoculation" theories.}, language = {en} } @article{WittFrankGillesetal.2018, author = {Witt, Stephanie H. and Frank, Josef and Gilles, Maria and Lang, Maren and Treutlein, Jens and Streit, Fabian and Wolf, Isabell A. C. and Peus, Verena and Scharnholz, Barbara and Send, Tabea S. and Heilmann-Heimbach, Stefanie and Sivalingam, Sugirthan and Dukal, Helene and Strohmaier, Jana and S{\"u}tterlin, Marc and Arloth, Janine and Laucht, Manfred and N{\"o}then, Markus M. and Deuschle, Michael and Rietschel, Marcella}, title = {Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation}, series = {BMC genomics}, volume = {19}, journal = {BMC genomics}, publisher = {BMC}, address = {London}, issn = {1471-2164}, doi = {10.1186/s12864-018-4652-7}, pages = {10}, year = {2018}, abstract = {Background: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. Methods: Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. Results: Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top "smoking methylation pattern" genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. Conclusion: The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight.}, language = {en} } @article{GillesOttoWolfetal.2018, author = {Gilles, Maria and Otto, Henrike and Wolf, Isabell A. C. and Scharnholz, Barbara and Peus, Verena and Schredl, Michael and Suetterlin, Marc W. and Witt, Stephanie H. and Rietschel, Marcella and Laucht, Manfred and Deuschle, Michael}, title = {Maternal hypothalamus-pituitary-adrenal (HPA) system activity and stress measures at birth}, series = {Psychoneuroendocrinology}, volume = {94}, journal = {Psychoneuroendocrinology}, publisher = {Elsevier}, address = {Oxford}, issn = {0306-4530}, doi = {10.1016/j.psyneuen.2018.04.022}, pages = {152 -- 161}, year = {2018}, abstract = {Background: Prenatal maternal stress might be a risk for the developing fetus and may have long-lasting effects on child and adult vulnerability to somatic and psychiatric disease. Over-exposure of the unborn to excess glucocorticoids and subsequent alteration of fetal development is hypothesized to be one of the key mechanisms linking prenatal stress with negative child outcome. Methods: In this prospective longitudinal study, mothers-to-be (n = 405) in late pregnancy (36.8 +/- 1.9 weeks of gestational age) and their singleton neonates were studied. We investigated the impact of different prenatal stress indices derived from six stress variables (perceived stress, specific prenatal worries, negative life events, symptoms of depression, trait anxiety, neuroticism) and diurnal maternal saliva cortisol secretion on gestational age and anthropometric measures at birth.}, language = {en} } @article{MillenetLauchtHohmetal.2018, author = {Millenet, Sabina and Laucht, Manfred and Hohm, Erika and Jennen-Steinmetz, Christine and Hohmann, Sarah and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Brandeis, Daniel and Zohsel, Katrin}, title = {Sex-specific trajectories of ADHD symptoms from adolescence to young adulthood}, series = {European child and adolescent psychiatry : offical journal of the European Society for Child and Adolescent Psychiatry}, volume = {27}, journal = {European child and adolescent psychiatry : offical journal of the European Society for Child and Adolescent Psychiatry}, number = {8}, publisher = {Springer}, address = {New York}, issn = {1018-8827}, doi = {10.1007/s00787-018-1129-9}, pages = {1067 -- 1075}, year = {2018}, abstract = {Reports of current ADHD symptoms in adults with a childhood diagnosis of ADHD are often discrepant: While one subgroup reports a particularly high level of current ADHD symptoms, another reports—in contrast—a very low level. The reasons for this difference remain unclear. Although sex might play a moderating role, it has not yet been examined in this regard. In an epidemiological cohort study from birth to young adulthood, childhood ADHD diagnoses were assessed at the ages of 4.5, 8, and 11 years based on parent ratings. Sex-specific development of ADHD symptoms was analyzed from the age of 15 to 25 years via self-reported ADHD symptoms in participants with (n = 47) and without childhood ADHD (n = 289) using a random coefficient regression model. The congruence between parent reports and adolescents' self-ratings was examined, and the role of childhood ADHD diagnosis, childhood OCC/CD, and childhood internalizing disorder as possible sex-specific predictors of self-reported ADHD symptoms at age 25 years was investigated. With regard to self-reported ADHD symptoms, females with a childhood ADHD diagnosis reported significantly more ADHD symptoms compared to females without childhood ADHD and males with and without ADHD throughout adolescence and young adulthood. In contrast, males with childhood ADHD did not differ from control males either at age 15 or at age 25 years. Only in females did a childhood diagnosis of an externalizing disorder (ADHD and CD/ODD) predict self-reported ADHD symptoms by age 25 years. Our findings suggest that self-reports of young adults with a childhood diagnosis of ADHD are influenced by sex. Specifically, females with childhood ADHD report increased levels of ADHD symptoms upon reaching adulthood. To correctly evaluate symptoms and impairment in this subgroup, other, more objective, sources of information may be advisable, such as neurophysiological measures.}, language = {en} } @article{SendBardtkeGillesetal.2018, author = {Send, Tabea Sarah and Bardtke, Svenja and Gilles, Maria and Wolf, Isabella Germaine and S{\"u}tterlin, Marc W. and Kirschbaum, Clemens and Laucht, Manfred and Witt, Stephanie H. and Rietschel, Marcella and Streit, Fabian and Deuschle, Michael}, title = {Stress reactivity in preschool-aged children}, series = {Psychoneuroendocrinology}, volume = {101}, journal = {Psychoneuroendocrinology}, publisher = {Elsevier}, address = {Oxford}, issn = {0306-4530}, doi = {10.1016/j.psyneuen.2018.11.002}, pages = {223 -- 231}, year = {2018}, abstract = {Prenatal maternal stress is an established risk factor for somatic and psychological health of the offspring. A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in offspring has been suggested as an important mechanism. However, the impact of prenatal stress on stress reactivity in preschool-aged children is not yet well understood. This is partly due to the fact that for this age group there is no stress test as well established as for older children and adults. In the present work a previously published stress test (Kryski et al., 2011) was evaluated in a large sample of 45-month-old children (n = 339). Furthermore, the relation between measures of prenatal maternal stress and cortisol reactivity was investigated. Prenatal stress was defined as psychopathology (self-report available for n = 339; expert-rating available for a subsample of n = 246) and perceived stress (n = 244) during pregnancy. The stress paradigm elicited significant increases in salivary cortisol 30 and 40 min after the test, and 60.8\% of the children were classified as responders. Lower cortisol levels after the stress test were observed in the group of children with prenatal stress defined as maternal psychopathology (both self-reported and expert-rated). Maternal perceived stress as a continuous measure was not significantly associated with cortisol levels. However, when comparing children in the highest quartile of maternal perceived stress to all other children, significantly lower cortisol values were observed in the prenatally stressed group. The present study confirms the paradigm by Kryski et al. as an effective stress test for preschool-aged children. Moreover, it provides further evidence that prenatal stress impacts HPA axis reactivity. Future studies should target the timing, nature, and intensity of prenatal stressors and their effect on the stress response in offspring at different developmental stages.}, language = {en} } @article{BoeckerSchlierHolzHohmetal.2017, author = {Boecker-Schlier, Regina and Holz, Nathalie E. and Hohm, Erika and Zohsel, Katrin and Blomeyer, Dorothea and Buchmann, Arlette F. and Baumeister, Sarah and Wolf, Isabella and Esser, G{\"u}nter and Schmidt, Martin H. and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Association between pubertal stage at first drink and neural reward processing in early adulthood}, series = {Addiction biology}, volume = {22}, journal = {Addiction biology}, publisher = {Wiley}, address = {Hoboken}, issn = {1355-6215}, doi = {10.1111/adb.12413}, pages = {1402 -- 1415}, year = {2017}, abstract = {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.}, language = {en} } @article{McLoughlinPalmerMakeigetal.2017, author = {McLoughlin, Grainne and Palmer, Jason and Makeig, Scott and Bigdely-Shamlo, Nima and Banaschewski, Tobias and Laucht, Manfred and Brandeis, D.}, title = {EEG Source Imaging Indices of Cognitive Control Show Associations with Dopamine System Genes}, series = {Brain Topography}, volume = {31}, journal = {Brain Topography}, number = {3}, publisher = {Springer}, address = {Dordrecht}, issn = {0896-0267}, doi = {10.1007/s10548-017-0601-z}, pages = {392 -- 406}, year = {2017}, abstract = {Cognitive or executive control is a critical mental ability, an important marker of mental illness, and among the most heritable of neurocognitive traits. Two candidate genes, catechol-O-methyltransferase (COMT) and DRD4, which both have a roles in the regulation of cortical dopamine, have been consistently associated with cognitive control. Here, we predicted that individuals with the COMT Met/Met allele would show improved response execution and inhibition as indexed by event-related potentials in a Go/NoGo task, while individuals with the DRD4 7-repeat allele would show impaired brain activity. We used independent component analysis (ICA) to separate brain source processes contributing to high-density EEG scalp signals recorded during the task. As expected, individuals with the DRD4 7-repeat polymorphism had reduced parietal P3 source and scalp responses to response (Go) compared to those without the 7-repeat. Contrary to our expectation, the COMT homozygous Met allele was associated with a smaller frontal P3 source and scalp response to response-inhibition (NoGo) stimuli, suggesting that while more dopamine in frontal cortical areas has advantages in some tasks, it may also compromise response inhibition function. An interaction effect emerged for P3 source responses to Go stimuli. These were reduced in those with both the 7-repeat DRD4 allele and either the COMT Val/Val or the Met/Met homozygous polymorphisms but not in those with the heterozygous Val/Met polymorphism. This epistatic interaction between DRD4 and COMT replicates findings that too little or too much dopamine impairs cognitive control. The anatomic and functional separated maximally independent cortical EEG sources proved more informative than scalp channel measures for genetic studies of brain function and thus better elucidate the complex mechanisms in psychiatric illness.}, language = {en} } @article{HohmZohselSchmidtetal.2017, author = {Hohm, Erika and Zohsel, Katrin and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Beeintr{\"a}chtigter Start ins Leben}, series = {Kindheit und Entwicklung}, volume = {26}, journal = {Kindheit und Entwicklung}, publisher = {Hogrefe}, address = {G{\"o}ttingen}, issn = {0942-5403}, doi = {10.1026/0942-5403/a000234}, pages = {210 -- 220}, year = {2017}, abstract = {Postpartale Depressionen sind h{\"a}ufige und schwerwiegende psychische Erkrankungen mit ung{\"u}nstigem Einfluss auf die kindliche Entwicklung. Als Haupttransmissionsweg gilt die fr{\"u}he Mutter-Kind-Interaktion. {\"U}ber die langfristigen Auswirkungen auf die Kinder im Erwachsenenalter und die Rolle der Interaktion liegen kaum Ergebnisse vor. Im Rahmen der Mannheimer Risikokinderstudie wurden postpartale Depressionen bis zwei Jahre nach der Geburt erfasst. Die kindliche Entwicklung wurde fortlaufend und die Mutter-Kind-Interaktion im Alter von 3 Monaten standardisiert erhoben. 28 Kinder postpartal depressiver und 107 Kinder gesunder M{\"u}tter konnten mit 25 Jahren untersucht werden. Beeintr{\"a}chtigungen der kognitiven und psychischen Entwicklung bei Kindern postpartal depressiver M{\"u}tter waren bis ins Erwachsenenalter nachweisbar. Responsives bzw. sensitives m{\"u}tterliches Verhalten wirkte der negativen Entwicklung entgegen. Dies betont die Bedeutung einer hohen Qualit{\"a}t der Mutter-Kind-Interaktion f{\"u}r die Entwicklung von Risikokindern.}, language = {de} } @article{ZohselHohmSchmidtetal.2017, author = {Zohsel, Katrin and Hohm, Erika and Schmidt, Martin H. and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Die langfristigen Auswirkungen von Fr{\"u}hgeburtlichkeit auf kognitive Entwicklung und Schulerfolg}, series = {Kindheit und Entwicklung}, volume = {26}, journal = {Kindheit und Entwicklung}, publisher = {Hogrefe}, address = {G{\"o}ttingen}, issn = {0942-5403}, doi = {10.1026/0942-5403/a000235}, pages = {221 -- 229}, year = {2017}, abstract = {In einer prospektiven L{\"a}ngsschnittstudie wurde der Zusammenhang zwischen fr{\"u}her Responsivit{\"a}t der Mutter und kognitiver Entwicklung ihrer fr{\"u}h- bzw. reifgeborenen Kinder untersucht. Im Alter von drei Monaten wurde daf{\"u}r die Mutter-Kind-Interaktion mittels Verhaltensbeobachtung erfasst. Bei n=351 der teilnehmenden Kinder (101 fr{\"u}hgeboren) wurde die allgemeine Intelligenz (IQ) im Alter von 11 Jahren und bei n=313 (85 fr{\"u}hgeboren) zus{\"a}tzlich der h{\"o}chste erreichte Schulabschluss bis 25 Jahren erhoben. Fr{\"u}hgeborene wiesen mit 11 Jahren einen signifikant niedrigeren IQ als Reifgeborene auf, nachdem f{\"u}r m{\"o}gliche konfundierende Faktoren kontrolliert worden war. Nur bei Fr{\"u}h-, nicht aber bei Reifgeborenen zeigte sich ein signifikanter positiver Zusammenhang zwischen m{\"u}tterlicher Responsivit{\"a}t und IQ. F{\"u}r die Wahrscheinlichkeit einen h{\"o}heren Schulabschluss (mind. Fachabitur) zu erreichen, fand sich weder ein signifikanter Effekt von Fr{\"u}hgeburtlichkeit noch von m{\"u}tterlicher Responsivit{\"a}t.}, language = {de} } @article{HohmLauchtZohseletal.2017, author = {Hohm, Erika and Laucht, Manfred and Zohsel, Katrin and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias}, title = {Resilienz und Ressourcen im Verlauf der Entwicklung}, series = {Kindheit und Entwicklung}, volume = {26}, journal = {Kindheit und Entwicklung}, publisher = {Hogrefe}, address = {G{\"o}ttingen}, issn = {0942-5403}, doi = {10.1026/0942-5403/a000236}, pages = {230 -- 239}, year = {2017}, abstract = {Anhand von Daten der Mannheimer Risikokinderstudie, die sich mit der langfristigen Entwicklung von Kindern mit unterschiedlichen Risikobelastungen besch{\"a}ftigt, wird gezeigt, wie Schutzfaktoren aufseiten des Kindes und seines famili{\"a}ren Umfelds im Verlauf der Entwicklung wirksam werden und zur Entstehung von Resilienz beitragen k{\"o}nnen. Eine besondere Rolle kommt dabei positiven fr{\"u}hen Eltern-Kind-Beziehungen zu (sowohl Mutter- als auch Vater-Kind-Interaktionen). Daneben spielen auch Interaktionserfahrungen im Alter von zwei Jahren des Kindes eine bedeutsame Rolle; diese sch{\"u}tzen Risikokinder davor, eine ung{\"u}nstige Entwicklung zu nehmen und tragen dazu bei, dass sich Kinder, die in psychosozialen Hochrisikofamilien aufwachsen, trotz ung{\"u}nstiger „Startbedingungen" positiv entwickeln. Neben Merkmalen der sozialen Umwelt nehmen auch sprachliche, sozial-emotionale und internale Kompetenzen des Kindes im Entwicklungsverlauf eine wichtige Rolle ein. Diese Kompetenzen erm{\"o}glichen es Risikokindern auch unter widrigen Lebensumst{\"a}nden (psychosoziale Hochrisikofamilien, Aufwachsen in Armutsverh{\"a}ltnissen) erfolgreich zu bestehen. Dar{\"u}ber hinaus zeigt die Arbeit, dass Resilienz ein Pers{\"o}nlichkeitsmerkmal ist, das ab dem fr{\"u}hen Erwachsenenalter eine hohe Stabilit{\"a}t besitzt. Mit diesen Befunden verweist die Arbeit auf die große Bedeutung der Resilienz bei der Vorhersage der langfristigen Entwicklung von Risikokindern.}, language = {de} } @misc{HohmZohselSchmidtetal.2017, author = {Hohm, Erika and Zohsel, Katrin and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Beeintr{\"a}chtigter Start ins Leben}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {692}, issn = {1866-8364}, doi = {10.25932/publishup-43340}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-433406}, pages = {37}, year = {2017}, abstract = {Postpartale Depressionen sind h{\"a}ufige und schwerwiegende psychische Erkrankungen mit ung{\"u}nstigem Einfluss auf die kindliche Entwicklung. Als Haupttransmissionsweg gilt die fr{\"u}he Mutter-Kind-Interaktion. {\"U}ber die langfristigen Auswirkungen auf die Kinder im Erwachsenenalter und die Rolle der Interaktion liegen kaum Ergebnisse vor. Im Rahmen der Mannheimer Risikokinderstudie wurden postpartale Depressionen bis zwei Jahre nach der Geburt erfasst. Die kindliche Entwicklung wurde fortlaufend und die Mutter-Kind-Interaktion im Alter von 3 Monaten standardisiert erhoben. 28 Kinder postpartal depressiver und 107 Kinder gesunder M{\"u}tter konnten mit 25 Jahren untersucht werden. Beeintr{\"a}chtigungen der kognitiven und psychischen Entwicklung bei Kindern postpartal depressiver M{\"u}tter waren bis ins Erwachsenenalter nachweisbar. Responsives bzw. sensitives m{\"u}tterliches Verhalten wirkte der negativen Entwicklung entgegen. Dies betont die Bedeutung einer hohen Qualit{\"a}t der Mutter-Kind-Interaktion f{\"u}r die Entwicklung von Risikokindern.}, language = {de} } @misc{ZohselHohmSchmidtetal.2017, author = {Zohsel, Katrin and Hohm, Erika and Schmidt, Martin H. and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Langfristige Folgen fr{\"u}her psychosozialer Risiken}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {609}, issn = {1866-8364}, doi = {10.25932/publishup-43342}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-433424}, pages = {203 -- 209}, year = {2017}, abstract = {In einer prospektiven L{\"a}ngsschnittstudie wurden Auswirkungen fr{\"u}her psychosozialer Risiken bis ins junge Erwachsenenalter untersucht und dabei die Rolle von affektiver und behavioraler Dysregulation im Kindesalter als vermittelndem Faktor {\"u}berpr{\"u}ft. Drei Monate nach der Geburt wurde das Vorliegen von 11 psychosozialen Belastungsfaktoren erfasst. Im Alter von 8 - 15 Jahren wurde dreimal das Child Behavior Checklist-Dysregulationsprofil (CBCL-DP) erhoben. Mit 25 Jahren wurde ein Strukturiertes Klinisches Interview durchgef{\"u}hrt und 309 der Teilnehmer f{\"u}llten den Young Adult Self-Report aus. Fr{\"u}he psychosoziale Risiken gingen mit einem erh{\"o}hten Risiko f{\"u}r das Vorliegen eines Substanzmissbrauchs im jungen Erwachsenenalter sowie mit erh{\"o}htem externalisierendem und internalisierendem Problemverhalten einher. Der Zusammenhang zwischen fr{\"u}hen psychosozialen Risiken und sp{\"a}terem externalisierendem bzw. internalisierendem Problemverhalten wurde durch das CBCL-DP vermittelt.}, language = {de} } @misc{HohmLauchtZohseletal.2017, author = {Hohm, Erika and Laucht, Manfred and Zohsel, Katrin and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias}, title = {Resilienz und Ressourcen im Verlauf der Entwicklung}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {608}, issn = {1866-8364}, doi = {10.25932/publishup-43307}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-433072}, pages = {230 -- 239}, year = {2017}, abstract = {Anhand von Daten der Mannheimer Risikokinderstudie, die sich mit der langfristigen Entwicklung von Kindern mit unterschiedlichen Risikobelastungen besch{\"a}ftigt, wird gezeigt, wie Schutzfaktoren aufseiten des Kindes und seines famili{\"a}ren Umfelds im Verlauf der Entwicklung wirksam werden und zur Entstehung von Resilienz beitragen k{\"o}nnen. Eine besondere Rolle kommt dabei positiven fr{\"u}hen Eltern-Kind-Beziehungen zu (sowohl Mutter- als auch Vater-Kind-Interaktionen). Daneben spielen auch Interaktionserfahrungen im Alter von zwei Jahren des Kindes eine bedeutsame Rolle; diese sch{\"u}tzen Risikokinder davor, eine ung{\"u}nstige Entwicklung zu nehmen und tragen dazu bei, dass sich Kinder, die in psychosozialen Hochrisikofamilien aufwachsen, trotz ung{\"u}nstiger „Startbedingungen" positiv entwickeln. Neben Merkmalen der sozialen Umwelt nehmen auch sprachliche, sozial-emotionale und internale Kompetenzen des Kindes im Entwicklungsverlauf eine wichtige Rolle ein. Diese Kompetenzen erm{\"o}glichen es Risikokindern auch unter widrigen Lebensumst{\"a}nden (psychosoziale Hochrisikofamilien, Aufwachsen in Armutsverh{\"a}ltnissen) erfolgreich zu bestehen. Dar{\"u}ber hinaus zeigt die Arbeit, dass Resilienz ein Pers{\"o}nlichkeitsmerkmal ist, das ab dem fr{\"u}hen Erwachsenenalter eine hohe Stabilit{\"a}t besitzt. Mit diesen Befunden verweist die Arbeit auf die große Bedeutung der Resilienz bei der Vorhersage der langfristigen Entwicklung von Risikokindern.}, language = {de} } @misc{ZohselHohmSchmidtetal.2017, author = {Zohsel, Katrin and Hohm, Erika and Schmidt, Martin H. and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Die langfristigen Auswirkungen von Fr{\"u}hgeburtlichkeit auf kognitive Entwicklung und Schulerfolg}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {701}, issn = {1866-8364}, doi = {10.25932/publishup-43353}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-433536}, pages = {11}, year = {2017}, abstract = {In einer prospektiven L{\"a}ngsschnittstudie wurde der Zusammenhang zwischen fr{\"u}her Responsivit{\"a}t der Mutter und kognitiver Entwicklung ihrer fr{\"u}h- bzw. reifgeborenen Kinder untersucht. Im Alter von drei Monaten wurde daf{\"u}r die Mutter-Kind-Interaktion mittels Verhaltensbeobachtung erfasst. Bei n=351 der teilnehmenden Kinder (101 fr{\"u}hgeboren) wurde die allgemeine Intelligenz (IQ) im Alter von 11 Jahren und bei n=313 (85 fr{\"u}hgeboren) zus{\"a}tzlich der h{\"o}chste erreichte Schulabschluss bis 25 Jahren erhoben. Fr{\"u}hgeborene wiesen mit 11 Jahren einen signifikant niedrigeren IQ als Reifgeborene auf, nachdem f{\"u}r m{\"o}gliche konfundierende Faktoren kontrolliert worden war. Nur bei Fr{\"u}h-, nicht aber bei Reifgeborenen zeigte sich ein signifikanter positiver Zusammenhang zwischen m{\"u}tterlicher Responsivit{\"a}t und IQ. F{\"u}r die Wahrscheinlichkeit einen h{\"o}heren Schulabschluss (mind. Fachabitur) zu erreichen, fand sich weder ein signifikanter Effekt von Fr{\"u}hgeburtlichkeit noch von m{\"u}tterlicher Responsivit{\"a}t.}, language = {de} } @article{ZohselHolzHohmetal.2017, author = {Zohsel, Katrin and Holz, Nathalie E. and Hohm, Erika and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Fewer self-reported depressive symptoms in young adults exposed to maternal depressed mood during pregnancy}, series = {Journal of Affective Disorders}, volume = {209}, journal = {Journal of Affective Disorders}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0165-0327}, doi = {10.1016/j.jad.2016.08.059}, pages = {155 -- 162}, year = {2017}, abstract = {Background: Depressed mood is prevalent during pregnancy, with accumulating evidence suggesting an impact on developmental outcome in the offspring. However, the long-term effects of prenatal maternal depression regarding internalizing psychopathology in the offspring are as yet unclear. Results: In n=85 young adults exposed to prenatal maternal depressed mood, no significantly higher risk for a diagnosis of depressive disorder was observed. However, they reported significantly lower levels of depressive symptoms. This association was especially pronounced when prenatal maternal depressed mood was present during the first trimester of pregnancy and when maternal mood was depressed pre- as well as postnatally. At an uncorrected level only, prenatal maternal depressed mood was associated with decreased amygdala volume. Limitations: Prenatal maternal depressed mood was not assessed during pregnancy, but shortly after childbirth. No diagnoses of maternal clinical depression during pregnancy were available. Conclusions: Self-reported depressive symptoms do not imply increased, but rather decreased symptom levels in young adults who were exposed to prenatal maternal depressed mood. A long-term perspective may be important when considering consequences of prenatal risk factors.}, 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{ZohselHohmSchmidtetal.2017, author = {Zohsel, Katrin and Hohm, Erika and Schmidt, Martin H. and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Long-Term Consequences of Early Psychosocial Risks}, series = {Kindheit und Entwicklung}, volume = {26}, journal = {Kindheit und Entwicklung}, number = {4}, publisher = {Hogrefe}, address = {G{\"o}ttingen}, issn = {0942-5403}, doi = {10.1026/0942-5403/a000233}, pages = {203 -- 209}, year = {2017}, abstract = {In einer prospektiven L{\"a}ngsschnittstudie wurden Auswirkungen fr{\"u}her psychosozialer Risiken bis ins junge Erwachsenenalter untersucht und dabei die Rolle von affektiver und behavioraler Dysregulation im Kindesalter als vermittelndem Faktor {\"u}berpr{\"u}ft. Drei Monate nach der Geburt wurde das Vorliegen von 11 psychosozialen Belastungsfaktoren erfasst. Im Alter von 8 - 15 Jahren wurde dreimal das Child Behavior Checklist-Dysregulationsprofil (CBCL-DP) erhoben. Mit 25 Jahren wurde ein Strukturiertes Klinisches Interview durchgef{\"u}hrt und 309 der Teilnehmer f{\"u}llten den Young Adult Self-Report aus. Fr{\"u}he psychosoziale Risiken gingen mit einem erh{\"o}hten Risiko f{\"u}r das Vorliegen eines Substanzmissbrauchs im jungen Erwachsenenalter sowie mit erh{\"o}htem externalisierendem und internalisierendem Problemverhalten einher. Der Zusammenhang zwischen fr{\"u}hen psychosozialen Risiken und sp{\"a}terem externalisierendem bzw. internalisierendem Problemverhalten wurde durch das CBCL-DP vermittelt.}, language = {de} } @article{PitzerEsserSchmidtetal.2017, author = {Pitzer, Martina and Esser, G{\"u}nter and Schmidt, Martin H. and Hohm, Erika and Banaschewski, Tobias and Laucht, Manfred}, title = {Child regulative temperament as a mediator of parenting in the development of depressive symptoms}, series = {Journal of neural transmission}, volume = {124}, journal = {Journal of neural transmission}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-017-1682-2}, pages = {631 -- 641}, year = {2017}, abstract = {Child temperament as well as parenting behaviors have been linked to adolescent depression. Beyond their main effects, the interplay between these factors is of interest. For example, in an interactive model, a differential susceptibility of temperamental variants to parenting has been suggested. However, so far, the differential susceptibility hypothesis has mostly been studied with a focus on externalizing disorders. On the other hand, parenting may shape the child's temperament and vice versa in a transactional process. In a prospective, longitudinal at-risk sample (163 boys, 176 girls), we assessed emotional (easy-difficult) and regulative (self-control) temperament at ages 4.5, and 8 years, respectively, as well as parenting quality at age 4.5 years using the HOME inventory. Hierarchical linear regression analysis was used to investigate the prediction of depressive symptoms at age 11, measured by the Child Depression Inventory, including interaction terms between the temperament variable and parenting. We additionally tested whether parenting was mediated by child temperament. As previously reported, both self-control and parenting were longitudinally associated with preadolescent depressive symptoms. There were no interactive effects between temperament and parenting. However, the effects of parenting were partly mediated by self-control. Our data do not support a differential susceptibility of temperamental variants in the development of preadolescent depression. However, our results are in line with the assumption that parenting may shape young children's temperament, with positive parenting in the early childhood fostering the development of regulative temperament.}, language = {en} } @article{SendGillesCoddetal.2017, author = {Send, Tabea Sarah and Gilles, Maria and Codd, Veryan and Wolf, Isabell and Bardtke, Svenja and Streit, Fabian and Strohmaier, Jana and Frank, Josef and Schendel, Darja and Suetterlin, Mark W. and Denniff, Matthew and Laucht, Manfred and Samani, Nilesh J. and Deuschle, Michael and Rietschel, Marcella and Witt, Stephanie H.}, title = {Telomere Length in Newborns is Related to Maternal Stress During Pregnancy}, series = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {42}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, publisher = {Nature Publ. Group}, address = {London}, issn = {0893-133X}, doi = {10.1038/npp.2017.73}, pages = {2407 -- 2413}, year = {2017}, abstract = {Telomere length (TL) is a marker of biological aging, and numerous studies have shown associations between TL and somatic or psychiatric disorders. Research also indicates an association between maternal stress during pregnancy and TL in the offspring. The present study investigated possible associations between TL and: (1) maternal perceived stress during pregnancy; (2) a maternal lifetime history of psychiatric disorder (lifetime PD); and (3) paternal age. TL was analyzed in 319 newborns and 318 mothers from a predominantly Caucasian sample (n= 273 Caucasian newborns and n= 274 Caucasian mothers). Two key findings were observed. First, maternal perceived stress during pregnancy was associated with shorter telomeres in newborns but not with maternal TL. Second, maternal lifetime PD was associated with shorter maternal telomeres, but not with TL in newborns. Paternal age was not associated with TL in newborns. The finding that maternal stress during pregnancy is associated with shorter telomeres in newborns supports the results of smaller previous studies. The fact that a relation between maternal prenatal stress and TL was observed in the offspring but not in mothers may be attributable to a high vulnerability to stress during intrauterine development of a maturing organism. To our knowledge, this is the largest study to date to show that maternal stress during pregnancy but not maternal lifetime PD is associated with shorter telomeres in the offspring.}, language = {en} } @article{WolfGillesPeusetal.2017, author = {Wolf, Isabell Ann-Cathrin and Gilles, Maria and Peus, Verena and Scharnholz, Barbara and Seibert, Julia and Jennen-Steinmetz, Christine and Krumm, Bertram and Deuschle, Michael and Laucht, Manfred}, title = {Impact of prenatal stress on the dyadic behavior of mothers and their 6-month-old infants during a play situation: role of different dimensions of stress}, series = {Journal of neural transmission}, volume = {124}, journal = {Journal of neural transmission}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-017-1770-3}, pages = {1251 -- 1260}, year = {2017}, language = {en} } @article{HolzBoeckerSchlierBuchmannetal.2017, author = {Holz, Nathalie E. and Boecker-Schlier, Regina and Buchmann, Arlette F. and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Baumeister, Sarah and Plichta, Michael M. and Cattrell, Anna and Schumann, Gunter and Esser, G{\"u}nter and Schmidt, Martin and Buitelaar, Jan and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder}, series = {Frontiers in human neuroscience}, volume = {12}, journal = {Frontiers in human neuroscience}, number = {2}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1749-5016}, doi = {10.1093/scan/nsw120}, pages = {261 -- 272}, year = {2017}, abstract = {Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2-19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years). CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors.}, language = {en} } @article{EsserReichWageneretal.2017, author = {Esser, G{\"u}nter and Reich, Stefanie and Wagener, Nina and H{\"o}sch, Ingrid and Ihle, Wolfgang and Laucht, Manfred}, title = {PoKI: Potsdamer Kinder-Interview f{\"u}r 6- bis 12-J{\"a}hrige}, publisher = {Hogrefe}, address = {G{\"o}ttingen}, pages = {57}, year = {2017}, language = {de} } @article{HolzZohselLauchtetal.2016, author = {Holz, Nathalie E. and Zohsel, Katrin and Laucht, Manfred and Banaschewski, Tobias and Hohmann, Sarah and Brandeis, Daniel}, title = {Gene x environment interactions in conduct disorder}, series = {Neuroscience \& biobehavioral reviews : official journal of the International Behavioral Neuroscience Society}, volume = {91}, journal = {Neuroscience \& biobehavioral reviews : official journal of the International Behavioral Neuroscience Society}, publisher = {Elsevier}, address = {Oxford}, issn = {0149-7634}, doi = {10.1016/j.neubiorev.2016.08.017}, pages = {239 -- 258}, year = {2016}, abstract = {Conduct disorder (CD) causes high financial and social costs, not only in affected families but across society, with only moderately effective treatments so far. There is consensus that CD is likely caused by the convergence of many different factors, including genetic and adverse environmental factors. There is ample evidence of gene-environment interactions in the etiology of CD on a behavioral level regarding genetically sensitive designs and candidate gene-driven approaches, most prominently and consistently represented by MAOA. However, conclusive indications of causal GxE patterns are largely lacking. Inconsistent findings, lack of replication and methodological limitations remain a major challenge. Likewise, research addressing the identification of affected brain pathways which reflect plausible biological mechanisms underlying GxE is still very sparse. Future research will have to take multilevel approaches into account, which combine genetic, environmental, epigenetic, personality, neural and hormone perspectives. A better understanding of relevant GxE patterns in the etiology of CD might enable researchers to design customized treatment options (e.g. biofeedback interventions) for specific subgroups of patients.}, language = {en} } @article{HolzBoeckerSchlierJennenSteinmetzetal.2016, author = {Holz, Nathalie E. and Boecker-Schlier, Regina and Jennen-Steinmetz, Christine and Buchmann, Arlette F. and Blomeyer, Dorothea and Baumeister, Sarah and Plichta, Michael M. and Esser, G{\"u}nter and Schmidt, Martin and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Positive coping styles and perigenual ACC volume: two related mechanisms for conferring resilience?}, series = {Frontiers in human neuroscience}, volume = {11}, journal = {Frontiers in human neuroscience}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1749-5016}, doi = {10.1093/scan/nsw005}, pages = {813 -- 820}, year = {2016}, abstract = {Stress exposure has been linked to increased rates of depression and anxiety in adults, particularly in females, and has been associated with maladaptive changes in the anterior cingulate cortex (ACC), which is an important brain structure involved in internalizing disorders. Coping styles are important mediators of the stress reaction by establishing homeostasis, and may thus confer resilience to stress-related psychopathology. Anatomical scans were acquired in 181 healthy participants at age 25 years. Positive coping styles were determined using a self-report questionnaire (German Stress Coping Questionnaire, SVF78) at age 22 years. Adult anxiety and depression symptoms were assessed at ages 22, 23 and 25 years with the Young Adult Self-Report. Information on previous internalizing diagnoses was obtained by diagnostic interview (2-19 years). Positive coping styles were associated with increased ACC volume. ACC volume and positive coping styles predicted anxiety and depression in a sex-dependent manner with increased positive coping and ACC volume being related to lower levels of psychopathology in females, but not in males. These results remained significant when controlled for previous internalizing diagnoses. These findings indicate that positive coping styles and ACC volume are two linked mechanisms, which may serve as protective factors against internalizing disorders.}, language = {en} } @article{ZohselBaldusSchmidtetal.2016, author = {Zohsel, Katrin and Baldus, Christiane and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Thomasius, Rainer and Laucht, Manfred}, title = {Predicting later problematic cannabis use from psychopathological symptoms during childhood and adolescence: Results of a 25-year longitudinal study}, series = {Drug and alcohol dependence : an international journal on biomedical and psychosocial approaches}, volume = {163}, journal = {Drug and alcohol dependence : an international journal on biomedical and psychosocial approaches}, publisher = {Elsevier}, address = {Clare}, issn = {0376-8716}, doi = {10.1016/j.drugalcdep.2016.04.012}, pages = {251 -- 255}, year = {2016}, abstract = {Background: Cannabis is the most commonly used illegal substance among adolescents and young adults. Problematic cannabis use is often associated with comorbid psychopathological problems. The purpose of the current study was to elucidate the underlying developmental processes connecting externalizing and internalizing psychopathology in childhood and adolescence with problematic cannabis use in young adulthood. Methods: Data were drawn from the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study from birth to adulthood. For n = 307 participants, symptom scores of conduct/oppositional defiant disorder, attention problems, hyperactivity/impulsivity, and internalizing disorders were available for the periods of childhood (4.5-11 years) and adolescence (15 years). At age 25 years, problematic cannabis use was assessed via clinical interview and a self-rating questionnaire. Results: At age 25 years, problematic cannabis use was identified in n = 28 participants (9.1\%). Childhood conduct/oppositional behavior problems were predictive of problematic cannabis use during young adulthood when comorbid symptoms were controlled for. No such effect was found for childhood attention, hyperactivity/impulsivity or internalizing problems. With respect to psychopathological symptoms during adolescence, only attention problems were significantly related to later problematic cannabis use when controlling for comorbidity. Conclusions: The current study highlights the role of conduct/oppositional behavior problems during childhood and attention problems during adolescence in later problematic cannabis use. It sheds more light on the developmental sequence of childhood and adolescence psychopathology and young adult cannabis use, which is a prerequisite for effective prevention approaches. (C) 2016 Elsevier Ireland Ltd. All rights reserved.}, language = {en} } @article{HolzBoeckerSchlierBuchmannetal.2016, author = {Holz, Nathalie and Boecker-Schlier, Regina and Buchmann, Arlette F. and Blomeyer, Dorothea and Baumeister, Sarah and Hohmann, Sarah and Jennen-Steinmetz, Christine and Wolf, Isabella and Rietschel, Marcella and Witt, Stephanie H. and Plichta, Michael M. and Meyer-Lindenberg, Andreas and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Evidence for a Sex-Dependent MAOAx Childhood Stress Interaction in the Neural Circuitry of Aggression}, series = {Cerebral cortex}, volume = {26}, journal = {Cerebral cortex}, publisher = {Oxford Univ. Press}, address = {Cary}, issn = {1047-3211}, doi = {10.1093/cercor/bhu249}, pages = {904 -- 914}, year = {2016}, abstract = {Converging evidence emphasizes the role of an interaction between monoamine oxidase A (MAOA) genotype, environmental adversity, and sex in the pathophysiology of aggression. The present study aimed to clarify the impact of this interaction on neural activity in aggression-related brain systems. Functional magnetic resonance imaging was performed in 125 healthy adults from a high-risk community sample followed since birth. DNA was genotyped for the MAOA-VNTR (variable number of tandem repeats). Exposure to childhood life stress (CLS) between the ages of 4 and 11 years was assessed using a standardized parent interview, aggression by the Youth/Young Adult Self-Report between the ages of 15 and 25 years, and the VIRA-R (Vragenlijst Instrumentele En Reactieve Agressie) at the age of 15 years. Significant interactions were obtained between MAOA genotype, CLS, and sex relating to amygdala, hippocampus, and anterior cingulate cortex (ACC) response, respectively. Activity in the amygdala and hippocampus during emotional face-matching increased with the level of CLS in male MAOA-L, while decreasing in male MAOA-H, with the reverse pattern present in females. Findings in the opposite direction in the ACC during a flanker NoGo task suggested that increased emotional activity coincided with decreased inhibitory control. Moreover, increasing amygdala activity was associated with higher Y(A)SR aggression in male MAOA-L and female MAOA-H carriers. Likewise, a significant association between amygdala activity and reactive aggression was detected in female MAOA-H carriers. The results point to a moderating role of sex in the MAOAx CLS interaction for intermediate phenotypes of emotional and inhibitory processing, suggesting a possible mechanism in conferring susceptibility to violence-related disorders.}, language = {en} } @article{HohmannZohselBuchmannetal.2016, author = {Hohmann, Sarah and Zohsel, Katrin and Buchmann, Arlette F. and Blomeyer, Dorothea and Holz, Nathalie and Boecker-Schlier, Regina and Jennen-Steinmetz, Christine and Rietschel, Marcella and Witt, Stephanie H. and Schmidt, Martin H. and Esser, G{\"u}nter and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Hohm, Erika and Laucht, Manfred}, title = {Interacting effect of MAOA genotype and maternal prenatal smoking on aggressive behavior in young adulthood}, series = {Journal of neural transmission}, volume = {123}, journal = {Journal of neural transmission}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-016-1582-x}, pages = {885 -- 894}, year = {2016}, abstract = {Findings on the etiology of aggressive behavior have provided evidence for an effect both of genetic factors, such as variation in the monoamine oxidase A (MAOA) gene, and adverse environmental factors. Recent studies have supported the existence of gene × environment interactions, with early experiences playing a key role. In the present study, the effects of prenatal nicotine exposure, MAOA genotype and their interaction on aggressive behavior during young adulthood were examined. In a sample of 272 young adults (129 males, 143 females) from an epidemiological cohort study, smoking during pregnancy was measured with a standardized parent interview at the offspring's age of 3 months. Aggressive behavior was assessed between the ages of 19 and 25 years using the Young Adult Self-Report. DNA was genotyped for the MAOA 5\&\#8242; untranslated region variable number of tandem repeats polymorphism (VNTR). Results revealed a significant interaction between MAOA and smoking during pregnancy, indicating higher levels of aggressive behavior in young adults carrying the MAOA low-expressing genotype who had experienced prenatal nicotine exposure (n = 8, p = .025). In contrast, in carriers of the MAOA high-expressing genotype, maternal smoking during pregnancy had no effect on aggressive behavior during young adulthood (n = 20, p = .145). This study extends earlier findings demonstrating an interaction between MAOA genotype and prenatal nicotine exposure on aggressive behavior into young adulthood. The results point to the long-term adverse effects of smoking during pregnancy on the offspring's mental health, possibly underlining the importance of smoking cessation during pregnancy. According to the nature of the study (particularly sample size and power), analyses are exploratory and results need to be interpreted cautiously.}, language = {en} } @article{BoeckerSchlierHolzBuchmannetal.2016, author = {Boecker-Schlier, Regina and Holz, Nathalie E. and Buchmann, Arlette F. and Blomeyer, Dorothea and Plichta, Michael M. and Jennen-Steinmetz, Christine and Wolf, Isabella and Baumeister, Sarah and Treutleind, Jens and Rietschel, Marcella and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Interaction between COMT Val(158)Met polymorphism and childhood adversity affects reward processing in adulthood}, series = {NeuroImage : a journal of brain function}, volume = {132}, journal = {NeuroImage : a journal of brain function}, publisher = {Elsevier}, address = {San Diego}, issn = {1053-8119}, doi = {10.1016/j.neuroimage.2016.02.006}, pages = {556 -- 570}, year = {2016}, abstract = {Background: Accumulating evidence suggests that altered dopamine transmission may increase the risk of mental disorders such as ADHD, schizophrenia or depression, possibly mediated by reward system dysfunction. This study aimed to clarify the impact of the COMT Val(158)Met polymorphism in interaction with environmental variation (G x E) on neuronal activity during reward processing. Methods: 168 healthy young adults from a prospective study conducted over 25 years participated in amonetary incentive delay task measured with simultaneous EEG-fMRI. DNA was genotyped for COMT, and childhood family adversity (CFA) up to age 11 was assessed by a standardized parent interview. Results: At reward delivery, a G x E revealed that fMRI activation for win vs. no-win trials in reward-related regions increased with the level of CFA in Met homozygotes as compared to Val/Met heterozygotes and Val homozygotes, who showed no significant effect. During the anticipation of monetary vs. verbal rewards, activation decreased with the level of CFA, which was also observed for EEG, in which the CNV declined with the level of CFA. Conclusions: These results identify convergent genetic and environmental effects on reward processing in a prospective study. Moreover, G x E effects during reward delivery suggest that stress during childhood is associated with higher reward sensitivity and reduced efficiency in processing rewarding stimuli in genetically at-risk individuals. Together with previous evidence, these results begin to define a specific system mediating interacting effects of early environmental and genetic risk factors, which may be targeted by early intervention and prevention. (C) 2016 Elsevier Inc. All rights reserved.}, language = {en} } @article{HolzBuchmannBoeckerSchlieretal.2015, author = {Holz, Nathalie E. and Buchmann, Arlette F. and Boecker-Schlier, Regina and Blomeyer, Dorothea and Baumeister, Sarah and Wolf, Isabella and Rietschel, Marcella and Witt, Stephanie H. and Plichta, Michael M. and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume}, series = {Brain structure \& function}, volume = {220}, journal = {Brain structure \& function}, number = {3}, publisher = {Springer}, address = {Heidelberg}, issn = {1863-2653}, doi = {10.1007/s00429-014-0729-5}, pages = {1355 -- 1368}, year = {2015}, abstract = {Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of FKBP5 in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders.}, language = {en} } @article{HeinrichBuchmannZohseletal.2015, author = {Heinrich, Angela and Buchmann, Arlette F. and Zohsel, Katrin and Dukal, Helene and Frank, Josef and Treutlein, Jens and Nieratschker, Vanessa and Witt, Stephanie H. and Brandeis, Daniel and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred and Rietschel, Marcella}, title = {Alterations of Glucocorticoid Receptor Gene Methylation in Externalizing Disorders During Childhood and Adolescence}, series = {Behavior genetics : an international journal devoted to research in the inheritance of behavior in animals and man}, volume = {45}, journal = {Behavior genetics : an international journal devoted to research in the inheritance of behavior in animals and man}, number = {5}, publisher = {Springer}, address = {New York}, issn = {0001-8244}, doi = {10.1007/s10519-015-9721-y}, pages = {529 -- 536}, year = {2015}, abstract = {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.}, language = {en} } @article{AdamoBaumeisterHohmannetal.2015, author = {Adamo, Nicoletta and Baumeister, Sarah and Hohmann, Sarah and Wolf, Isabella and Holz, Nathalie and Boecker-Schlier, Regina and Laucht, Manfred and Banaschewski, Tobias and Brandeis, Daniel}, title = {Frequency-specific coupling between trial-to-trial fluctuations of neural responses and response-time variability}, series = {Journal of neural transmission}, volume = {122}, journal = {Journal of neural transmission}, number = {8}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-015-1382-8}, pages = {1197 -- 1202}, year = {2015}, abstract = {We assessed intra-individual variability of response times (RT) and single-trial P3 amplitudes following targets in healthy adults during a Flanker/NO-GO task. RT variability and variability of the neural responses coupled at the faster frequencies examined (0.07-0.17 Hz) at Pz, the target-P3 maxima, despite non-significant associations for overall variability (standard deviation, SD). Frequency-specific patterns of variability in the single-trial P3 may help to understand the neurophysiology of RT variability and its explanatory models of attention allocation deficits beyond intra-individual variability summary indices such as SD.}, language = {en} } @article{PoustkaZohselBlomeyeretal.2015, author = {Poustka, Luise and Zohsel, Katrin and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Schmid, Brigitte and Trautmann-Villalba, Patricia and Hohmann, Sarah and Becker, Katja and Esser, G{\"u}nter and Schmidt, Martin H. and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Interacting effects of maternal responsiveness, infant regulatory problems and dopamine D4 receptor gene in the development of dysregulation during childhood: A longitudinal analysis}, series = {Journal of psychiatric research}, volume = {70}, journal = {Journal of psychiatric research}, publisher = {Elsevier}, address = {Oxford}, issn = {0022-3956}, doi = {10.1016/j.psychires.2015.08.018}, pages = {83 -- 90}, year = {2015}, abstract = {Recent longitudinal studies have indicated that affective and behavioral dysregulation in childhood is associated with an increased risk for various negative outcomes in later life. However, few studies to date have examined early mechanisms preceding dysregulation during early childhood. Aim of this study was to elucidate early mechanisms relating to dysregulation in later life using data from an epidemiological cohort study on the long-term outcome of early risk factors from birth to adulthood. At age 3 months, mothers and infants were videotaped during a nursing and playing situation. Maternal responsiveness was evaluated by trained raters. Infant regulatory problems were assessed on the basis of a parent interview and direct observation by trained raters. At age 8 and 11 years, 290 children (139 males) were rated on the Child Behavior Checklist (CBCL). Additionally, participants were genotyped for the dopamine D4 receptor (DRD4) exon 3 VNTR polymorphism. A significant three-way interaction between maternal responsiveness, DRD4 genotype and infant regulatory problems was detected predicting the CBCL-dysregulation profile (CBCL-DP). Carriers of the DRD4 7r allele with regulatory problems at age 3 months showed significantly more behavior problems associated with the CBCL-DP during childhood when exposed to less maternal responsiveness. In contrast, no effect of maternal responsiveness was observed in DRD4 7r carriers without infant regulatory problems and in non-carriers of the DRD4 7r allele. This prospective longitudinal study extends earlier findings regarding the association of the CBCL-DP with early parenting and later psychopathology, introducing both DRD4 genotype and infant regulatory problems as important moderators. (C) 2015 Elsevier Ltd. All rights reserved.}, language = {en} } @article{BenderBanaschewskiRoessneretal.2015, author = {Bender, Stephan and Banaschewski, Tobias and R{\"o}ßner, Veit and Klein, Christoph and Rietschel, Marcella and Feige, Bernd and Brandeis, Daniel and Laucht, Manfred}, title = {Variability of single trial brain activation predicts fluctuations in reaction time}, series = {Biological psychology}, volume = {106}, journal = {Biological psychology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0301-0511}, doi = {10.1016/j.biopsycho.2015.01.013}, pages = {50 -- 60}, year = {2015}, abstract = {Brain activation stability is crucial to understanding attention lapses. EEG methods could provide excellent markers to assess neuronal response variability with respect to temporal (intertrial coherence) and spatial variability (topographic consistency) as well as variations in activation intensity (low frequency variability of single trial global field power). We calculated intertrial coherence, topographic consistency and low frequency amplitude variability during target P300 in a continuous performance test in 263 15-year-olds from a cohort with psychosocial and biological risk factors. Topographic consistency and low frequency amplitude variability predicted reaction time fluctuations (RTSD) in a linear model. Higher RTSD was only associated with higher psychosocial adversity in the presence of the homozygous 6R-10R dopamine transporter haplotype. We propose that topographic variability of single trial P300 reflects noise as well as variability in evoked cortical activation patterns. Dopaminergic neuromodulation interacted with environmental and biological risk factors to predict behavioural reaction time variability. (C) 2015 Elsevier B.V. All rights reserved.}, language = {en} } @article{HohmannHohmTreutleinetal.2015, author = {Hohmann, Sarah and Hohm, Erika and Treutlein, Jens and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Association of norepinephrine transporter (NET, SLC6A2) genotype with ADHD-related phenotypes: Findings of a longitudinal study from birth to adolescence}, series = {Psychiatry research : the official publication of the International Society for Neuroimaging in Psychiatry}, volume = {226}, journal = {Psychiatry research : the official publication of the International Society for Neuroimaging in Psychiatry}, number = {2-3}, publisher = {Elsevier}, address = {Clare}, issn = {0165-1781}, doi = {10.1016/j.psychres.2014.12.029}, pages = {425 -- 433}, year = {2015}, abstract = {Variation in the gene encoding for the norepinephrine transporter (NET, SLC6A2) has repeatedly been linked with ADHD, although there is some inconsistency regarding the association with specific genes. The variants for which most consistent association has been found are the NET variants rs3785157 and rs28386840. Here, we tested for their association with ADHD diagnosis and ADHD-related phenotypes during development in a longitudinal German community sample. Children were followed from age 4 to age 15, using diagnostic interviews to assess ADHD. Between the ages of 8 and 15 years, the Child Behavior Checklist (CBCL) was administered to the primary caregivers. The continuous performance task (CPT) was performed at age 15. Controlling for possible confounders, we found that homozygous carriers of the major A allele of the functional promoter variant rs28386840 displayed a higher rate of ADHD lifetime diagnosis. Moreover, homozygous carriers of the minor T allele of rs3785157 were more likely to develop ADHD and showed higher scores on the CBCL externalizing behavior scales. Additionally, we found that individuals heterozygous for rs3785157 made fewer omission errors in the CPT than homozygotes. This is the first longitudinal study to report associations between specific NET variants and ADHD-related phenotypes during the course of development. (C) 2015 Elsevier Ireland Ltd. All rights reserved.}, language = {en} } @article{BuchmannHohmWittetal.2015, author = {Buchmann, Arlette F. and Hohm, Erika and Witt, Stephanie H. and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Role of CNR1 polymorphisms in moderating the effects of psychosocial adversity on impulsivity in adolescents}, series = {Journal of neural transmission}, volume = {122}, journal = {Journal of neural transmission}, number = {3}, publisher = {Springer}, address = {Wien}, issn = {0300-9564}, doi = {10.1007/s00702-014-1266-3}, pages = {455 -- 463}, year = {2015}, abstract = {Enhanced endocannabinoid signaling has been implicated in typically adolescent behavioral features such as increased risk-taking, impulsivity and novelty seeking. Research investigating the impact of genetic variants in the cannabinoid receptor 1 gene (CNR1) and of early rearing conditions has demonstrated that both factors contribute to the prediction of impulsivity-related phenotypes. The present study aimed to test the hypothesis of an interaction of the two most studied CNR1 polymorphisms rs806379 and rs1049353 with early psychosocial adversity in terms of affecting impulsivity in 15-year-olds from an epidemiological cohort sample followed since birth. In 323 adolescents (170 girls, 153 boys), problems of impulse control and novelty seeking were assessed using parent-report and self-report, respectively. Exposure to early psychosocial adversity was determined in a parent interview conducted at the age of 3 months. The results indicated that impulsivity increased following exposure to early psychosocial adversity, with this increase being dependent on CNR1 genotype. In contrast, while individuals exposed to early adversity scored higher on novelty seeking, no significant impact of genotype or the interaction thereof was detected. This is the first evidence to suggest that the interaction of CNR1 gene variants with the experience of early life adversity may play a role in determining adolescent impulsive behavior. However, given that the reported findings are obtained in a high-risk community sample, results are restricted in terms of interpretation and generalization. Future research is needed to replicate these findings and to identify the mediating mechanisms underlying this effect.}, language = {en} } @article{HolzBoeckerSchlierHohmetal.2015, author = {Holz, Nathalie E. and Boecker-Schlier, Regina and Hohm, Erika and Zohsel, Katrin and Buchmann, Arlette F. and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Baumeister, Sarah and Hohmann, Sarah and Wolf, Isabella and Plichta, Michael M. and Esser, G{\"u}nter and Schmidt, Martin and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {The Long-Term Impact of Early Life Poverty on Orbitofrontal Cortex Volume in Adulthood: Results from a Prospective Study Over 25 Years}, series = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {40}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, number = {4}, publisher = {Nature Publ. Group}, address = {London}, issn = {0893-133X}, doi = {10.1038/npp.2014.277}, pages = {996 -- 1004}, year = {2015}, abstract = {Converging evidence has highlighted the association between poverty and conduct disorder (CD) without specifying neurobiological pathways. Neuroimaging research has emphasized structural and functional alterations in the orbitofrontal cortex (OFC) as one key mechanism underlying this disorder. The present study aimed to clarify the long-term influence of early poverty on OFC volume and its association with CD symptoms in healthy participants of an epidemiological cohort study followed since birth. At age 25 years, voxel-based morphometry was applied to study brain volume differences. Poverty (0 = non-exposed (N = 134), I = exposed (N = 33)) and smoking during pregnancy were determined using a standardized parent interview, and information on maternal responsiveness was derived from videotaped mother infant interactions at the age of 3 months. CD symptoms were assessed by diagnostic interview from 8 to 19 years of age. Information on life stress was acquired at each assessment and childhood maltreatment was measured using retrospective self-report at the age of 23 years. Analyses were adjusted for sex, parental psychopathology and delinquency, obstetric adversity, parental education, and current poverty. Individuals exposed to early life poverty exhibited a lower OFC volume. Moreover, we replicated previous findings of increased CD symptoms as a consequence of childhood poverty. This effect proved statistically mediated by OFC volume and exposure to life stress and smoking during pregnancy, but not by childhood maltreatment and maternal responsiveness. These findings underline the importance of studying the impact of early life adversity on brain alterations and highlight the need for programs to decrease income-related disparities.}, 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} } @misc{BoeckerSchlierHolzBuchmannetal.2014, author = {Boecker-Schlier, Regina and Holz, Nathalie E. and Buchmann, Arlette F. and Blomeyer, Dorothea and Plichta, Michael M. and Wolf, Isabella and Baumeister, Sarah and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years}, series = {PLoS one}, volume = {9}, journal = {PLoS one}, number = {10}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0112155}, pages = {1}, year = {2014}, language = {en} } @article{NikitopoulosZohselBlomeyeretal.2014, author = {Nikitopoulos, Joerg and Zohsel, Katrin and Blomeyer, Dorothea and Buchmann, Arlette F. and Schmid, Brigitte and Jennen-Steinmetz, Christine and Becker, Katja and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Are infants differentially sensitive to parenting? Early maternal care, DRD4 genotype and externalizing behavior during adolescence}, series = {Journal of psychiatric research}, volume = {59}, journal = {Journal of psychiatric research}, publisher = {Elsevier}, address = {Oxford}, issn = {0022-3956}, doi = {10.1016/j.jpsychires.2014.08.012}, pages = {53 -- 59}, year = {2014}, language = {en} } @article{HolzBoeckerSchlierBaumeisteretal.2014, author = {Holz, Nathalie E. and Boecker-Schlier, Regina and Baumeister, Sarah and Hohm, Erika and Zohsel, Katrin and Buchmann, Arlette F. and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Hohmann, Sarah and Wolf, Isabella and Plichta, Michael M. and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Effect of prenatal exposure to tobacco smoke on inhibitory control neuroimaging results from a 25-Year prospective study}, series = {JAMA psychiatry}, volume = {71}, journal = {JAMA psychiatry}, number = {7}, publisher = {American Veterinary Medical Association}, address = {Chicago}, issn = {2168-622X}, doi = {10.1001/jamapsychiatry.2014.786}, pages = {786 -- 796}, year = {2014}, abstract = {IMPORTANCE: There is accumulating evidence relating maternal smoking during pregnancy to attention-deficit/hyperactivity disorder (ADHD) without elucidating specific mechanisms. Research investigating the neurobiological underpinnings of this disorder has implicated deficits during response inhibition. Attempts to uncover the effect of prenatal exposure to nicotine on inhibitory control may thus be of high clinical importance. MAIN OUTCOMES AND MEASURES: Functional magnetic resonance imaging response, morphometric data, lifetime ADHD symptoms, and novelty seeking. RESULTS: Participants prenatally exposed to nicotine exhibited a weaker response in the anterior cingulate cortex (t(168) = 4.46; peak Montreal Neurological Institute [MNI] coordinates x = -2, y = 20, z = 30; familywise error [FWE]-corrected P = .003), the right inferior frontal gyrus (t(168) = 3.65; peak MNI coordinates x = 44, y = 38, z = 12; FWE-corrected P = .04), the left inferior frontal gyrus (t(168) = 4.09; peak MNI coordinates x = -38, y = 36, z = 8; FWE-corrected P = .009), and the supramarginal gyrus (t(168) = 5.03; peak MNI coordinates x = 64, y = -28, z = 22; FWE-corrected P = .02) during the processing of the NoGo compared to neutral stimuli, while presenting a decreased volume in the right inferior frontal gyrus. These findings were obtained irrespective of the adjustment of confounders, ADHD symptoms, and novelty seeking. There was an inverse relationship between inferior frontal gyrus activity and ADHD symptoms and between anterior cingulate cortex activity and novelty seeking. CONCLUSIONS AND RELEVANCE: These findings point to a functional involvement of prenatal exposure to tobacco smoke in neural alterations similar to ADHD, which underlines the importance of smoking prevention treatments.}, 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} } @article{BuchmannZohselBlomeyeretal.2014, author = {Buchmann, Arlette F. and Zohsel, Katrin and Blomeyer, Dorothea and Hohm, Erika and Hohmann, Sarah and Jennen-Steinmetz, Christine and Treutlein, Jens and Becker, Katja and Banaschewski, Tobias and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Poustka, Luise and Zimmermann, Ulrich S. and Laucht, Manfred}, title = {Interaction between prenatal stress and dopamine D4 receptor genotype in predicting aggression and cortisol levels in young adults}, series = {Psychopharmacology}, volume = {231}, journal = {Psychopharmacology}, number = {16}, publisher = {Springer}, address = {New York}, issn = {0033-3158}, doi = {10.1007/s00213-014-3484-7}, pages = {3089 -- 3097}, year = {2014}, abstract = {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.}, language = {en} } @article{BoeckerSchlierHolzBuchmannetal.2014, author = {Boecker-Schlier, Regina and Holz, Nathalie E. and Buchmann, Arlette F. and Blomeyer, Dorothea and Plichta, Michael M. and Wolf, Isabella and Baumeister, Sarah and Meyer-Lindenberg, Andreas and Banaschewski, Tobias and Brandeis, Daniel and Laucht, Manfred}, title = {Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years}, series = {PLoS one}, volume = {9}, journal = {PLoS one}, number = {8}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0104185}, pages = {13}, year = {2014}, abstract = {Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58\% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway.}, language = {en} } @article{ZohselBuchmannBlomeyeretal.2014, author = {Zohsel, Katrin and Buchmann, Arlette F. and Blomeyer, Dorothea and Hohm, Erika and Schmidt, Martin H. and Esser, G{\"u}nter and Brandeis, Daniel and Banaschewski, Tobias and Laucht, Manfred}, title = {Mothers' prenatal stress and their children's antisocial outcomes - a moderating role for the dopamine receptor D4 (DRD4) gene}, series = {The journal of child psychology and psychiatry}, volume = {55}, journal = {The journal of child psychology and psychiatry}, number = {1}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0021-9630}, doi = {10.1111/jcpp.12138}, pages = {69 -- 76}, year = {2014}, abstract = {ResultsUnder conditions of elevated prenatal maternal stress, children carrying one or two DRD4 7r alleles were at increased risk of a diagnosis of CD/ODD. Moreover, homozygous carriers of the DRD4 7r allele displayed more externalizing behavior following exposure to higher levels of prenatal maternal stress, while homozygous carriers of the DRD4 4r allele turned out to be insensitive to the effects of prenatal stress. ConclusionsThis study is the first to report a gene-environment interaction related to DRD4 and prenatal maternal stress using data from a prospective study, which extends earlier findings on the impact of prenatal maternal stress with respect to childhood antisocial behavior.}, language = {en} } @article{BlomeyerFriemelBuchmannetal.2013, author = {Blomeyer, Dorothea and Friemel, Chris M. and Buchmann, Arlette F. and Banaschewski, Tobias and Laucht, Manfred and Schneider, Miriam}, title = {Impact of pubertal stage at first drink on adult drinking behavior}, series = {Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism}, volume = {37}, journal = {Alcoholism : clinical and experimental research ; the official journal of the American Medical Society on Alcoholism and the Research Society on Alcoholism}, number = {10}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0145-6008}, doi = {10.1111/acer.12154}, pages = {1804 -- 1811}, year = {2013}, abstract = {BackgroundEarly alcohol use is one of the strongest predictors of later alcohol use disorders, with early use usually taking place during puberty. Many researchers have suggested drinking during puberty as a potential biological basis of the age at first drink (AFD) effect. However, the influence of the pubertal phase at alcohol use initiation on subsequent drinking in later life has not been examined so far. MethodsPubertal stage at first drink (PSFD) was determined in N=283 young adults (131 males, 152 females) from an epidemiological cohort study. At ages 19, 22, and 23years, drinking behavior (number of drinking days, amount of alcohol consumed, hazardous drinking) was assessed using interview and questionnaire methods. Additionally, an animal study examined the effects of pubertal or adult ethanol (EtOH) exposure on voluntary EtOH consumption in later life in 20 male Wistar rats. ResultsPSFD predicted drinking behavior in humans in early adulthood, indicating that individuals who had their first drink during puberty displayed elevated drinking levels compared to those with postpubertal drinking onset. These findings were corroborated by the animal study, in which rats that received free access to alcohol during the pubertal period were found to consume more alcohol as adults, compared to the control animals that first came into contact with alcohol during adulthood. ConclusionsThe results point to a significant role of stage of pubertal development at first contact with alcohol for the development of later drinking habits. Possible biological mechanisms and implications for prevention are discussed.}, language = {en} } @article{BuchmannBlomeyerJennenSteinmetzetal.2013, author = {Buchmann, Arlette F. and Blomeyer, Dorothea and Jennen-Steinmetz, Christine and Schmidt, Martin H. and Esser, G{\"u}nter and Banaschewski, Tobias and Laucht, Manfred}, title = {Early smoking onset may promise initial pleasurable sensations and later addiction}, series = {Addiction biology}, volume = {18}, journal = {Addiction biology}, number = {6}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1369-1600}, doi = {10.1111/j.1369-1600.2011.00377.x}, pages = {947 -- 954}, year = {2013}, abstract = {There is converging evidence suggesting a particular susceptibility to the addictive properties of nicotine among adolescents. The aim of the current study was to prospectively ascertain the relationship between age at first cigarette and initial smoking experiences, and to examine the combined effects of these characteristics of adolescent smoking behavior on adult smoking. It was hypothesized that the association between earlier age at first cigarette and later development of nicotine dependence may, at least in part, be attributable to differences in experiencing pleasurable early smoking sensations. Data were drawn from the participants of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study from birth to adulthood. Structured interviews at age 15, 19 and 22 years were conducted to assess the age at first cigarette, early smoking experiences and current smoking behavior in 213 young adults. In addition, the participants completed the Fagerstrom Test for Nicotine Dependence. Adolescents who smoked their first cigarette at an earlier age reported more pleasurable sensations from the cigarette, and they were more likely to be regular smokers at age 22. The age at first cigarette also predicted the number of cigarettes smoked and dependence at age 22. Thus, both the age of first cigarette and the pleasure experienced from the cigarette independently predicted aspects of smoking at age 22.}, 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} }