@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{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{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{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{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{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} } @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{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{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{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{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{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{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} }