TY  - JOUR
A1  - Holz, Nathalie E.
A1  - Boecker-Schlier, Regina
A1  - Jennen-Steinmetz, Christine
A1  - Hohm, Erika
A1  - Buchmann, Arlette F.
A1  - Blomeyer, Dorothea
A1  - Baumeister, Sarah
A1  - Plichta, Michael M.
A1  - Esser, Günter
A1  - Schmidt, Martin
A1  - Meyer-Lindenberg, Andreas
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Early maternal care may counteract familial liability for psychopathology in the reward circuitry
JF  - Social Cognitive and Affective Neuroscience
N2  - 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.
KW  - maternal care
KW  - ADHD
KW  - ventral striatum
KW  - fMRI
KW  - resilience
KW  - aggression
Y1  - 2018
U6  - https://doi.org/10.1093/scan/nsy087
SN  - 1749-5016
SN  - 1749-5024
VL  - 13
IS  - 11
SP  - 1191
EP  - 1201
PB  - Oxford Univ. Press
CY  - Oxford
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  - Zohsel, Katrin
A1  - Holz, Nathalie E.
A1  - Hohm, Erika
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Brandeis, Daniel
A1  - Banaschewski, Tobias
A1  - Laucht, Manfred
T1  - Fewer self-reported depressive symptoms in young adults exposed to maternal depressed mood during pregnancy
JF  - Journal of Affective Disorders
N2  - 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.
Y1  - 2016
U6  - https://doi.org/10.1016/j.jad.2016.08.059
SN  - 0165-0327
SN  - 1573-2517
VL  - 209
SP  - 155
EP  - 162
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Holz, Nathalie E.
A1  - Zohsel, Katrin
A1  - Laucht, Manfred
A1  - Banaschewski, Tobias
A1  - Hohmann, Sarah
A1  - Brandeis, Daniel
T1  - Gene x environment interactions in conduct disorder
BT  - Implications for future treatments
JF  - Neuroscience & biobehavioral reviews : official journal of the International Behavioral Neuroscience Society
N2  - 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.
KW  - Gene-environment interaction
KW  - Conduct disorder
KW  - Aggression
KW  - Externalizing behavior
KW  - fMRI
Y1  - 2016
U6  - https://doi.org/10.1016/j.neubiorev.2016.08.017
SN  - 0149-7634
SN  - 1873-7528
VL  - 91
SP  - 239
EP  - 258
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Holz, Nathalie E.
A1  - Buchmann, Arlette F.
A1  - Boecker-Schlier, Regina
A1  - Blomeyer, Dorothea
A1  - Baumeister, Sarah
A1  - Wolf, Isabella
A1  - Rietschel, Marcella
A1  - Witt, Stephanie H.
A1  - Plichta, Michael M.
A1  - Meyer-Lindenberg, Andreas
A1  - Banaschewski, Tobias
A1  - Brandeis, Daniel
A1  - Laucht, Manfred
T1  - Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume
JF  - Brain structure & function
N2  - 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.
KW  - FKBP5
KW  - Childhood adversity
KW  - Amygdala
KW  - fMRI
KW  - Connectivity
KW  - Voxel-based morphometry
Y1  - 2015
U6  - https://doi.org/10.1007/s00429-014-0729-5
SN  - 1863-2653
SN  - 1863-2661
VL  - 220
IS  - 3
SP  - 1355
EP  - 1368
PB  - Springer
CY  - Heidelberg
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  - 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  - 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  - 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  - 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  -