TY  - JOUR
A1  - Hohmann, S.
A1  - Buchmann, Arlette F.
A1  - Witt, S. H.
A1  - Rietschel, M.
A1  - Jennen-Steinmetz, Christine
A1  - Schmidt, M. H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Laucht, Manfred
T1  - Increasing association between a neuropeptide Y promoter polymorphism and body mass index during the course of development
JF  - Pediatric obesity
N2  - Objective: To investigate the association of the neuropeptide Y (NPY) promoter polymorphism rs16147 with body mass index (BMI) during the course of development from infancy to adulthood.
 Design: Longitudinal, prospective study of a German community sample.
 Subjects: n = 306 young adults (139 males, 167 females).
 Measurements: Participants' body weight and height were assessed at the ages of 3 months and 2, 4.5, 8, 11, 15 and 19 years. NPY rs16147 was genotyped.
 Results: Controlling for a number of possible confounders, homozygote carriers of the rs16147 C allele exhibited significantly lower BMI scores when compared with individuals carrying the T allele. In addition, a significant genotype by age interaction emerged, indicating that the genotype effect increased during the course of development.
 Conclusions: This is the first longitudinal study to report an association between rs16147 and BMI during childhood and adolescence. The finding that this effect increased during the course of development may either be due to age-dependent alterations in gene expression or to maturation processes within the weight regulation circuits of the central nervous system.
KW  - Development
KW  - neuropeptide Y
KW  - rs16147
KW  - weight regulation
Y1  - 2012
U6  - https://doi.org/10.1111/j.2047-6310.2012.00069.x
SN  - 2047-6310
VL  - 7
IS  - 6
SP  - 453
EP  - 460
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - GEN
A1  - Send, T. S.
A1  - Gilles, M.
A1  - Codd, V.
A1  - Wolf, I. A. C.
A1  - Bardtke, S.
A1  - Streit, Fabian
A1  - Strohmaier, Jana
A1  - Frank, Josef
A1  - Schendel, D.
A1  - Sutterlin, M. W.
A1  - Denniff, M.
A1  - Laucht, Manfred
A1  - Samani, N. J.
A1  - Deuschle, Michael
A1  - Rietschel, Marcella
A1  - Witt, Stephanie H.
T1  - Telomere length in newborns is related to maternal stress during pregnancy Response
T2  - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
KW  - Predictive markers
KW  - Risk factors
Y1  - 2018
U6  - https://doi.org/10.1038/s41386-018-0079-8
SN  - 0893-133X
SN  - 1740-634X
VL  - 43
IS  - 11
SP  - 2164
EP  - 2164
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Send, Tabea
A1  - Bardtke, S.
A1  - Gilles, M.
A1  - Wolf, I. A. C.
A1  - Sütterlin, Marc Wolf
A1  - Wudy, S. A.
A1  - Wang, R.
A1  - Laucht, Manfred
A1  - Witt, Stephanie H.
A1  - Rietschel, Marcella
A1  - Streit, Fabian
A1  - Deuschle, Michael
T1  - Prenatal maternal stress is associated with lower cortisol and cortisone levels in the first morning urine of 45-month-old children
JF  - Psychoneuroendocrinology
N2  - 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.
KW  - Prenatal stress
KW  - Cortisol
KW  - Cortisone
KW  - HPA axis
KW  - Perceived stress
KW  - Psychopathology
Y1  - 2019
U6  - https://doi.org/10.1016/j.psyneuen.2019.01.017
SN  - 0306-4530
VL  - 103
SP  - 219
EP  - 224
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Buchmann, Arlette F.
A1  - Hellweg, Rainer
A1  - Rietschel, Marcella
A1  - Treutlein, Jens
A1  - Witt, Stephanie H.
A1  - Zimmermann, Ulrich S.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Laucht, Manfred
A1  - Deuschle, Michael
T1  - BDNF Val 66 Met and 5-HTTLPR genotype moderate the impact of early psychosocial adversity on plasma brain-derived neurotrophic factor and depressive symptoms - a prospective study
JF  - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
N2  - Recent studies have emphasized an important role for neurotrophins, such as brain-derived neurotrophic factor (BDNF), in regulating the plasticity of neural circuits involved in the pathophysiology of stress-related diseases. The aim of the present study was to examine the interplay of the BDNF Val(66)Met and the serotonin transporter promoter (5-HTTLPR) polymorphisms in moderating the impact of early-life adversity on BDNF plasma concentration and depressive symptoms. Participants were taken from an epidemiological cohort study following the long-term outcome of early risk factors from birth into young adulthood. In 259 individuals (119 males, 140 females), genotyped for the BDNF Val(66)Met and the 5-HTTLPR polymorphisms, plasma BDNF was assessed at the age of 19 years. In addition, participants completed the Beck Depression Inventory (BDI). Early adversity was determined according to a family adversity index assessed at 3 months of age. Results indicated that individuals homozygous for both the BDNF Val and the 5-HTTLPR L allele showed significantly reduced BDNF levels following exposure to high adversity. In contrast, BDNF levels appeared to be unaffected by early psychosocial adversity in carriers of the BDNF Met or the 5-HTTLPR S allele. While the former group appeared to be most susceptible to depressive symptoms, the impact of early adversity was less pronounced in the latter group. This is the first preliminary evidence indicating that early-life adverse experiences may have lasting sequelae for plasma BDNF levels in humans, highlighting that the susceptibility to this effect is moderated by BDNF Val(66)Met and 5-HTTLPR genotype.
KW  - BDNF
KW  - 5-HTTLPR
KW  - Human
KW  - Early psychosocial adversity
KW  - Longitudinal study
KW  - Depression
Y1  - 2013
U6  - https://doi.org/10.1016/j.euroneuro.2012.09.003
SN  - 0924-977X
VL  - 23
IS  - 8
SP  - 902
EP  - 909
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Witt, Stephanie H.
A1  - Buchmann, Arlette F.
A1  - Blomeyer, Dorothea
A1  - Nieratschker, Vanessa
A1  - Treutlein, Jens
A1  - Esser, Günter
A1  - Schmidt, Martin H.
A1  - Bidlingmaier, Martin
A1  - Wiedemann, Klaus
A1  - Rietschel, Marcella
A1  - Laucht, Manfred
A1  - Wuest, Stefan
A1  - Zimmermann, Ulrich S.
T1  - An interaction between a neuropeptide Y gene polymorphism and early adversity modulates endocrine stress responses
JF  - Psychoneuroendocrinology
N2  - Interindividual variability in the regulation of the human stress system accounts for a part of the individual's liability to stress-related diseases. These differences are influenced by environmental and genetic factors. Early childhood adversity is a well-studied environmental factor affecting an individual's stress response which has been shown to be modulated by gene environment interaction (GxE). Neuropeptide Y (NPY) plays a role in stress regulation and genetic variation in NPY may influence stress responses. In this study, we analyzed the association of a common variant in the NPY gene promoter, rs16147, with cortisol and ACTH responses to acute psychosocial stress in young adults from the Mannheim Study of Children at Risk (MARS), an ongoing epidemiological cohort study following the outcome of early adversity from birth into adulthood. We found evidence of a GxE interaction between rs16147 and early adversity significantly affecting HPA axis responses to acute psychosocial stress. These findings suggest that the neurobiological mechanisms linking early adverse experience and later neuroendocrine stress regulation are modulated by a gene variant whose functional relevance is documented by increasing convergent evidence from in vitro, animal and human studies.
KW  - GxE interaction
KW  - Stress
KW  - HPA
KW  - Neuropeptide Y
KW  - Early adversity
Y1  - 2011
U6  - https://doi.org/10.1016/j.psyneuen.2010.12.015
SN  - 0306-4530
VL  - 36
IS  - 7
SP  - 1010
EP  - 1020
PB  - Elsevier
CY  - Oxford
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  - Witt, Stephanie H.
A1  - Frank, Josef
A1  - Gilles, Maria
A1  - Lang, Maren
A1  - Treutlein, Jens
A1  - Streit, Fabian
A1  - Wolf, Isabell A. C.
A1  - Peus, Verena
A1  - Scharnholz, Barbara
A1  - Send, Tabea S.
A1  - Heilmann-Heimbach, Stefanie
A1  - Sivalingam, Sugirthan
A1  - Dukal, Helene
A1  - Strohmaier, Jana
A1  - Sütterlin, Marc
A1  - Arloth, Janine
A1  - Laucht, Manfred
A1  - Nöthen, Markus M.
A1  - Deuschle, Michael
A1  - Rietschel, Marcella
T1  - Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation
JF  - BMC genomics
N2  - 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.
KW  - DNA methylation
KW  - Smoking
KW  - Birth weight
KW  - Mediation analysis
Y1  - 2018
U6  - https://doi.org/10.1186/s12864-018-4652-7
SN  - 1471-2164
VL  - 19
PB  - BMC
CY  - London
ER  - 
TY  - JOUR
A1  - Witt, B.
A1  - Bornhorst, Julia
A1  - Mitze, H.
A1  - Ebert, Franziska
A1  - Meyer, S.
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Arsenolipids exert less toxicity in a human neuron astrocyte co-culture as compared to the respective monocultures
JF  - Metallomics : integrated biometal science
N2  - Arsenic-containing hydrocarbons (AsHCs), natural products found in seafood, have recently been shown to exert toxic effects in human neurons. In this study we assessed the toxicity of three AsHCs in cultured human astrocytes. Due to the high cellular accessibility and substantial toxicity observed astrocytes were identified as further potential brain target cells for arsenolipids. Thereby, the AsHCs exerted a 5-19-fold higher cytotoxicity in astrocytes as compared to arsenite. Next we compared the toxicity of the arsenicals in a co-culture model of the respective human astrocytes and neurons. Notably the AsHCs did not show any substantial toxic effects in the co-culture, while arsenite did. The arsenic accessibility studies indicated that in the co-culture astrocytes protect neurons against cellular arsenic accumulation especially after incubation with arsenolipids. In summary, these data underline the importance of the glial-neuron interaction when assessing the in vitro neurotoxicity of new unclassified metal species.
Y1  - 2017
U6  - https://doi.org/10.1039/c7mt00036g
SN  - 1756-5901
SN  - 1756-591X
VL  - 9
SP  - 442
EP  - 446
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  -