TY  - JOUR
A1  - Adamo, Nicoletta
A1  - Baumeister, Sarah
A1  - Hohmann, Sarah
A1  - Wolf, Isabella
A1  - Holz, Nathalie
A1  - Boecker-Schlier, Regina
A1  - Laucht, Manfred
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
T1  - Frequency-specific coupling between trial-to-trial fluctuations of neural responses and response-time variability
JF  - Journal of neural transmission
N2  - 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.
KW  - Intra-individual response-time variability
KW  - Event-related potential
KW  - Cognitive control
KW  - Attention deficit
Y1  - 2015
U6  - https://doi.org/10.1007/s00702-015-1382-8
SN  - 0300-9564
SN  - 1435-1463
VL  - 122
IS  - 8
SP  - 1197
EP  - 1202
PB  - Springer
CY  - Wien
ER  - 
TY  - JOUR
A1  - Boecker-Schlier, Regina
A1  - Holz, Nathalie E.
A1  - Buchmann, Arlette F.
A1  - Blomeyer, Dorothea
A1  - Plichta, Michael M.
A1  - Jennen-Steinmetz, Christine
A1  - Wolf, Isabella
A1  - Baumeister, Sarah
A1  - Treutleind, Jens
A1  - Rietschel, Marcella
A1  - Meyer-Lindenberg, Andreas
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Interaction between COMT Val(158)Met polymorphism and childhood adversity affects reward processing in adulthood
JF  - NeuroImage : a journal of brain function
N2  - 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.
KW  - Reward processing
KW  - COMT Val(158)Met polymorphism
KW  - Childhood adversity
KW  - Gene-environment interaction
KW  - Functional magnetic resonance imaging
KW  - Electroencephalography
Y1  - 2016
U6  - https://doi.org/10.1016/j.neuroimage.2016.02.006
SN  - 1053-8119
SN  - 1095-9572
VL  - 132
SP  - 556
EP  - 570
PB  - Elsevier
CY  - San Diego
ER  - 
TY  - GEN
A1  - Boecker-Schlier, Regina
A1  - Holz, Nathalie E.
A1  - Buchmann, Arlette F.
A1  - Blomeyer, Dorothea
A1  - Plichta, Michael M.
A1  - Wolf, Isabella
A1  - Baumeister, Sarah
A1  - Meyer-Lindenberg, Andreas
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years
T2  - PLoS one
Y1  - 2014
U6  - https://doi.org/10.1371/journal.pone.0112155
SN  - 1932-6203
VL  - 9
IS  - 10
PB  - PLoS
CY  - San Fransisco
ER  - 
TY  - JOUR
A1  - Boecker-Schlier, Regina
A1  - Holz, Nathalie E.
A1  - Buchmann, Arlette F.
A1  - Blomeyer, Dorothea
A1  - Plichta, Michael M.
A1  - Wolf, Isabella
A1  - Baumeister, Sarah
A1  - Meyer-Lindenberg, Andreas
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years
JF  - PLoS one
N2  - 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.
Y1  - 2014
U6  - https://doi.org/10.1371/journal.pone.0104185
SN  - 1932-6203
VL  - 9
IS  - 8
PB  - PLoS
CY  - San Fransisco
ER  - 
TY  - JOUR
A1  - Boecker-Schlier, Regina
A1  - Holz, Nathalie E.
A1  - Hohm, Erika
A1  - Zohsel, Katrin
A1  - Blomeyer, Dorothea
A1  - Buchmann, Arlette F.
A1  - Baumeister, Sarah
A1  - Wolf, Isabella
A1  - Esser, Günter
A1  - Schmidt, Martin H.
A1  - Meyer-Lindenberg, Andreas
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Association between pubertal stage at first drink and neural reward processing in early adulthood
JF  - Addiction biology
N2  - Puberty is a critical time period during human development. It is characterized by high levels of risk-taking behavior, such as increased alcohol consumption, and is accompanied by various neurobiological changes. Recent studies in animals and humans have revealed that the pubertal stage at first drink (PSFD) significantly impacts drinking behavior in adulthood. Moreover, neuronal alterations of the dopaminergic reward system have been associated with alcohol abuse or addiction. This study aimed to clarify the impact of PSFD on neuronal characteristics of reward processing linked to alcohol-related problems. One hundred sixty-eight healthy young adults from a prospective study covering 25 years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. PSFD was determined according to the age at menarche or Tanner stage of pubertal development, respectively. Alcohol-related problems in early adulthood were assessed with the Alcohol Use Disorder Identification Test (AUDIT). During reward anticipation, decreased fMRI activation of the frontal cortex and increased preparatory EEG activity (contingent negative variation) occurred with pubertal compared to postpubertal first alcohol intake. Moreover, alcohol-related problems during early adulthood were increased in pubertal compared to postpubertal beginners, which was mediated by neuronal activation of the right medial frontal gyrus. At reward delivery, increased fMRI activation of the left caudate and higher feedback-related EEG negativity were detected in pubertal compared to postpubertal beginners. Together with animal findings, these results implicate PSFD as a potential modulator of psychopathology, involving altered reward anticipation. Both PSFD timing and reward processing might thus be potential targets for early prevention and intervention.
KW  - alcohol-related problems
KW  - electroencephalography
KW  - functional magnetic resonance imaging
KW  - puberty
KW  - reward processing
Y1  - 2017
U6  - https://doi.org/10.1111/adb.12413
SN  - 1355-6215
SN  - 1369-1600
VL  - 22
SP  - 1402
EP  - 1415
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Buchmann, Arlette F.
A1  - Holz, Nathalie
A1  - Boecker-Schlier, Regina
A1  - Blomeyer, Dorothea
A1  - Rietschel, Marcella
A1  - Witt, Stephanie H.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Zimmermann, Ulrich S.
A1  - Laucht, Manfred
T1  - Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood
JF  - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
N2  - Recent research suggests an important role of FKBP5, a glucocorticoid receptor regulating co-chaperone, in the development of stress-related diseases such as depression and anxiety disorders. The present study aimed to replicate and extend previous evidence indicating that FKBP5 polymorphisms moderate hypothalamus-pituitary-adrenal (HPA) function by examining whether FKBP5 rs1360780 genotype and different measures of childhood adversity interact to predict stress-induced cortisol secretion. At age 19 years, 195 young adults (90 males, 105 females) participating in an epidemiological cohort study completed the Trier Social Stress Test (TSST) to assess cortisol stress responsiveness and were genotyped for the FKBP5 rs1360780. Childhood adversity was assessed using the Childhood Trauma Questionnaire (CTQ) and by a standardized parent interview yielding an index of family adversity. A significant interaction between genotype and childhood adversity on cortisol response to stress was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report (CTQ), but not for prospectively ascertained objective family adversity. Severity of childhood maltreatment was significantly associated with attenuated cortisol levels among carriers of the rs1360780 CC genotype, while no such effect emerged in carriers of the T allele. These findings point towards the functional involvement of FKBP5 in long-term alterations of neuroendocrine stress regulation related to childhood maltreatment, which have been suggested to represent a premorbid risk or resilience factor in the context of stress-related disorders. (C) 2013 Elsevier B.V. and ECNR This is an open access article under the CC BY-NC-ND license.
KW  - FKBP5
KW  - Stress
KW  - HPA
KW  - Cortisol
KW  - Childhood adversity
Y1  - 2014
U6  - https://doi.org/10.1016/j.euroneuro.2013.12.001
SN  - 0924-977X
SN  - 1873-7862
VL  - 24
IS  - 6
SP  - 837
EP  - 845
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Hohmann, Sarah
A1  - Zohsel, Katrin
A1  - Buchmann, Arlette F.
A1  - Blomeyer, Dorothea
A1  - Holz, Nathalie
A1  - Boecker-Schlier, Regina
A1  - Jennen-Steinmetz, Christine
A1  - Rietschel, Marcella
A1  - Witt, Stephanie H.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Meyer-Lindenberg, Andreas
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Hohm, Erika
A1  - Laucht, Manfred
T1  - Interacting effect of MAOA genotype and maternal prenatal smoking on aggressive behavior in young adulthood
JF  - Journal of neural transmission
N2  - 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′ 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.
KW  - MAOA
KW  - Smoking during pregnancy
KW  - Interaction
KW  - Aggression
KW  - Longitudinal
KW  - Young adulthood
Y1  - 2016
U6  - https://doi.org/10.1007/s00702-016-1582-x
SN  - 0300-9564
SN  - 1435-1463
VL  - 123
SP  - 885
EP  - 894
PB  - Springer
CY  - Wien
ER  - 
TY  - JOUR
A1  - Holz, Nathalie
A1  - Boecker-Schlier, Regina
A1  - Buchmann, Arlette F.
A1  - Blomeyer, Dorothea
A1  - Baumeister, Sarah
A1  - Hohmann, Sarah
A1  - Jennen-Steinmetz, Christine
A1  - Wolf, Isabella
A1  - Rietschel, Marcella
A1  - Witt, Stephanie H.
A1  - Plichta, Michael M.
A1  - Meyer-Lindenberg, Andreas
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Evidence for a Sex-Dependent MAOAx Childhood Stress Interaction in the Neural Circuitry of Aggression
JF  - Cerebral cortex
N2  - 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.
KW  - aggression
KW  - amygdala
KW  - fMRI
KW  - life stress
KW  - MAOA
Y1  - 2016
U6  - https://doi.org/10.1093/cercor/bhu249
SN  - 1047-3211
SN  - 1460-2199
VL  - 26
SP  - 904
EP  - 914
PB  - Oxford Univ. Press
CY  - Cary
ER  - 
TY  - JOUR
A1  - Holz, Nathalie E.
A1  - Boecker-Schlier, Regina
A1  - Baumeister, Sarah
A1  - Hohm, Erika
A1  - Zohsel, Katrin
A1  - Buchmann, Arlette F.
A1  - Blomeyer, Dorothea
A1  - Jennen-Steinmetz, Christine
A1  - Hohmann, Sarah
A1  - Wolf, Isabella
A1  - Plichta, Michael M.
A1  - Meyer-Lindenberg, Andreas
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Effect of prenatal exposure to tobacco smoke on inhibitory control neuroimaging results from a 25-Year prospective study
JF  - JAMA psychiatry
N2  - 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.
Y1  - 2014
U6  - https://doi.org/10.1001/jamapsychiatry.2014.786
SN  - 2168-622X
SN  - 2168-6238
VL  - 71
IS  - 7
SP  - 786
EP  - 796
PB  - American Veterinary Medical Association
CY  - Chicago
ER  - 
TY  - JOUR
A1  - Holz, Nathalie E.
A1  - Boecker-Schlier, Regina
A1  - Buchmann, Arlette F.
A1  - Blomeyer, Dorothea
A1  - Jennen-Steinmetz, Christine
A1  - Baumeister, Sarah
A1  - Plichta, Michael M.
A1  - Cattrell, Anna
A1  - Schumann, Gunter
A1  - Esser, Günter
A1  - Schmidt, Martin
A1  - Buitelaar, Jan
A1  - Meyer-Lindenberg, Andreas
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder
JF  - Frontiers in human neuroscience
N2  - 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.
KW  - childhood adversity
KW  - conduct disorder
KW  - amygdala
KW  - ventral striatum
KW  - fMRI
Y1  - 2016
U6  - https://doi.org/10.1093/scan/nsw120
SN  - 1749-5016
SN  - 1749-5024
VL  - 12
IS  - 2
SP  - 261
EP  - 272
PB  - Oxford Univ. Press
CY  - Oxford
ER  -