TY  - JOUR
A1  - Laucht, Manfred
A1  - Treutlein, Jens
A1  - Schmid, Brigitte
A1  - Blomeyer, Dorothea
A1  - Becker, Katja
A1  - Buchmann, Arlette F.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Jennen-Steinmetz, Christine
A1  - Rietschel, Marcella
A1  - Zimmermann, Ulrich S.
A1  - Banaschewski, Tobias
T1  - Impact of psychosocial adversity on alcohol intake in young adults : moderation by the LL genotype of the serotonin transporter polymorphism
N2  - Background: Evidence from animal studies supports a role for serotonin transporter gene promoter polymorphism (5-HTTLPR) gene-environment interaction (G X E) in the development of excessive alcohol intake. Few studies in humans have been conducted on this topic, yielding inconsistent results. The present study aims to further explore G x E between 5-HTTLPR and exposure to psychosocial adversity on alcohol consumption in a high-risk community sample of young adults. Methods: Data were collected as part of the Mannheim Study of Children at Risk, an ongoing epidemiological cohort study following the outcome of early risk factors from birth into young adulthood. At age 19 years, 309 participants (142 male participants, 167 female participants) were genotyped for the biallelic and triallelic 5-HTTLPR and were administered a 45-day alcohol timeline follow-back interview, providing measures of the total number of drinks and the number of binge drinking days. Psychosocial adversity was assessed at birth (family adversity) and at age 19 (negative life events). Results: In contrast to various previous reports, a significant G x E emerged, indicating that, when exposed to high psychosocial adversity, individuals with the LL genotype of 5-HTTLPR exhibited more hazardous drinking than those carrying the S allele or those without exposure to adversity. This effect, which was confined to male participants, held both for different classifications of 5-HTTLPR and different types of adversity. Conclusions: One explanation for the discrepant results might be heterogeneity in alcohol phenotypes. While the L allele relates more strongly to early-onset alcoholism, the S allele may be linked more closely to alcohol use associated with anxiety and depression.
Y1  - 2009
UR  - http://www.sciencedirect.com/science/journal/00063223
U6  - https://doi.org/10.1016/j.biopsych.2009.02.010
SN  - 0006-3223
ER  - 
TY  - JOUR
A1  - Gulbins, Erich
A1  - Palmada, Monica
A1  - Reichel, Martin
A1  - Lueth, Anja
A1  - Boehmer, Christoph
A1  - Amato, Davide
A1  - Mueller, Christian P.
A1  - Tischbirek, Carsten H.
A1  - Groemer, Teja W.
A1  - Tabatabai, Ghazaleh
A1  - Becker, Katrin Anne
A1  - Tripal, Philipp
A1  - Staedtler, Sven
A1  - Ackermann, Teresa F.
A1  - van Brederode, Johannes
A1  - Alzheimer, Christian
A1  - Weller, Michael
A1  - Lang, Undine E.
A1  - Kleuser, Burkhard
A1  - Grassme, Heike
A1  - Kornhuber, Johannes
T1  - Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs
JF  - Nature medicine
N2  - Major depression is a highly prevalent severe mood disorder that is treated with antidepressants. The molecular targets of antidepressants require definition. We investigated the role of the acid sphingomyelinase (Asm)-ceramide system as a target for antidepressants. Therapeutic concentrations of the antidepressants amitriptyline and fluoxetine reduced Asm activity and ceramide concentrations in the hippocampus, increased neuronal proliferation, maturation and survival and improved behavior in mouse models of stress-induced depression. Genetic Asm deficiency abrogated these effects. Mice overexpressing Asm, heterozygous for acid ceramidase, treated with blockers of ceramide metabolism or directly injected with C16 ceramide in the hippocampus had higher ceramide concentrations and lower rates of neuronal proliferation, maturation and survival compared with controls and showed depression-like behavior even in the absence of stress. The decrease of ceramide abundance achieved by antidepressant-mediated inhibition of Asm normalized these effects. Lowering ceramide abundance may thus be a central goal for the future development of antidepressants.
Y1  - 2013
U6  - https://doi.org/10.1038/nm.3214
SN  - 1078-8956
VL  - 19
IS  - 7
SP  - 934
EP  - +
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - JOUR
A1  - Schmid, Brigitte
A1  - Blomeyer, Dorothea
A1  - Becker, Katja
A1  - Treutlein, Jens
A1  - Zimmermann, Ulrich S.
A1  - Buchmann, Arlette F.
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Rietschel, Marcella
A1  - Laucht, Manfred
T1  - The interaction between the dopamine transporter gene and age at onset in relation to tobacco and alcohol use among 19-year-olds
N2  - Recent evidence suggests that heterogeneity in the age at onset could explain the inconsistent findings of association studies relating the dopamine transporter (DAT1) gene with alcohol and nicotine consumption. The aim of this study was to examine interactions between two DAT1 polymorphisms and different initiation ages with regard to alcohol and tobacco consumption levels and dependence. Two hundred and ninety-one young adults (135 males, 156 females) participating in the Mannheim Study of Children at Risk were genotyped for the 40-bp variable number of tandem repeats (VNTR) and rs27072 polymorphisms of DAT1. Age at initiation was assessed at age 15 and 19 years. Information about current alcohol and tobacco consumption was obtained at age 19 years using self-report measures and structured interviews. Results suggest that age at onset of intensive consumption moderated the association of the DAT1 gene with early adult substance use and dependence, revealing a DAT1 effect only among individuals homozygous for the 10r allele of the 40-bp VNTR who had started daily smoking or being intoxicated early in life. Equally, carriers of the T allele of the rs27072 polymorphism reporting an early age at first intoxication showed higher current alcohol consumption at age 19 years. In contrast, no interaction between rs27072 and the age at first cigarette with regard to later smoking was observed. These findings provide evidence that the DAT1 gene interacts with an early heavy or regular drug exposure of the maturing adolescent brain to predict substance (ab)use in young adulthood. Further studies are required to confirm these findings.
Y1  - 2009
UR  - http://www3.interscience.wiley.com/cgi-bin/issn?DESCRIPTOR=PRINTISSN&VALUE=1355-6215
U6  - https://doi.org/10.1111/j.1369-1600.2009.00171.x
SN  - 1355-6215
ER  - 
TY  - JOUR
A1  - Nikitopoulos, Joerg
A1  - Zohsel, Katrin
A1  - Blomeyer, Dorothea
A1  - Buchmann, Arlette F.
A1  - Schmid, Brigitte
A1  - Jennen-Steinmetz, Christine
A1  - Becker, Katja
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Brandeis, Daniel
A1  - Banaschewski, Tobias
A1  - Laucht, Manfred
T1  - Are infants differentially sensitive to parenting? Early maternal care, DRD4 genotype and externalizing behavior during adolescence
JF  - Journal of psychiatric research
KW  - DRD4
KW  - Early maternal care
KW  - Externalizing behavior
KW  - Adolescence
KW  - Gene-environment interaction
Y1  - 2014
U6  - https://doi.org/10.1016/j.jpsychires.2014.08.012
SN  - 0022-3956
SN  - 1879-1379
VL  - 59
SP  - 53
EP  - 59
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Buchmann, Arlette F.
A1  - Zohsel, Katrin
A1  - Blomeyer, Dorothea
A1  - Hohm, Erika
A1  - Hohmann, Sarah
A1  - Jennen-Steinmetz, Christine
A1  - Treutlein, Jens
A1  - Becker, Katja
A1  - Banaschewski, Tobias
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Brandeis, Daniel
A1  - Poustka, Luise
A1  - Zimmermann, Ulrich S.
A1  - Laucht, Manfred
T1  - Interaction between prenatal stress and dopamine D4 receptor genotype in predicting aggression and cortisol levels in young adults
JF  - Psychopharmacology
N2  - Considerable evidence suggests that genetic factors combine with environmental influences to impact on the development of aggressive behavior. A genetic variant that has repeatedly been reported to render individuals more sensitive to the presence of adverse experiences, including stress exposure during fetal life, is the seven-repeat allele of the dopamine D4 receptor (DRD4) gene.
 The present investigation concentrated on the interplay of prenatal maternal stress and DRD4 genotype in predicting self-reported aggression in young adults. As disruption of the hypothalamic-pituitary-adrenal system has been discussed as a pathophysiological pathway to aggression, cortisol stress reactivity was additionally examined.
 As part of an epidemiological cohort study, prenatal maternal stress was assessed by maternal interview 3 months after childbirth. Between the ages of 19 and 23 years, 298 offspring (140 males, 158 females) completed the Young Adult Self-Report to measure aggressive behavior and were genotyped for the DRD4 gene. At 19 years, 219 participants additionally underwent the Trier Social Stress Test to determine cortisol reactivity.
 Extending earlier findings with respect to childhood antisocial behavior, the results revealed that, under conditions of higher prenatal maternal stress, carriers of the DRD4 seven-repeat allele displayed more aggression in adulthood (p = 0.032). Moreover, the same conditions which seemed to promote aggression were found to predict attenuated cortisol secretion (p = 0.028).
 This is the first study to indicate a long-term impact of prenatal stress exposure on the cortisol stress response depending on DRD4 genotype.
KW  - Prenatal stress
KW  - Aggression
KW  - Cortisol
KW  - DRD4
KW  - Gene-environment interaction
Y1  - 2014
U6  - https://doi.org/10.1007/s00213-014-3484-7
SN  - 0033-3158
SN  - 1432-2072
VL  - 231
IS  - 16
SP  - 3089
EP  - 3097
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Buchmann, Arlette F.
A1  - Schmid, Brigitte
A1  - Blomeyer, Dorothea
A1  - Becker, Katja
A1  - Treutlein, Jens
A1  - Zimmermann, Ulrich S.
A1  - Jennen-Steinmetz, Christine
A1  - Schmidt, Martin H.
A1  - Esser, Günter
A1  - Banaschewski, Tobias
A1  - Rietschel, Marcella
A1  - Schumann, Gunter
A1  - Laucht, Manfred
T1  - Impact of age at first drink on vulnerability to alcohol-related problems : testing the marker hypothesis in a prospective study of young adults
N2  - There is ample evidence that the early initiation of alcohol use is a risk factor for the development of later alcohol-related problems. The purpose of the current study was to examine whether this association can be explained by indicators of a common underlying susceptibility or whether age at drinking onset may be considered as an independent predictor of later drinking behavior, suggesting a potential causal relationship. Participants were drawn from a prospective cohort study of the long-term outcomes of early risk factors followed up from birth onwards. Structured interviews were administered to 304 participants to assess age at first drink and current drinking behavior. Data on risk factors, including early family adversity, parental alcohol use, childhood psychopathology and stressful life events, were repeatedly collected during childhood using standardized parent interviews. In addition, information on genotype was considered. Results confirmed previous work demonstrating that hazardous alcohol consumption is related to early-adolescent drinking onset. A younger age of first drink was significantly predicted by 5-HTTLPR genotype and the degree of preceding externalizing symptoms, and both factors were related to increased consumption or harmful alcohol use at age 19. However, even after controlling for these potential explanatory factors, earlier age at drinking onset remained a strong predictor of heavy alcohol consumption in young adulthood. The present longitudinal study adds to the current literature indicating that the early onset - adult hazardous drinking association cannot solely be attributed to shared genetic and psychopathologic risk factors as examined in this study.
Y1  - 2009
UR  - http://www.sciencedirect.com/science/journal/00223956
U6  - https://doi.org/10.1016/j.jpsychires.2009.02.006
SN  - 0022-3956
ER  - 
TY  - JOUR
A1  - Schwope, Axel
A1  - Pires, Adriana M.
A1  - Kurpas, Jan
A1  - Doroshenko, Victor
A1  - Suleimanov, Valery F.
A1  - Freyberg, Michael
A1  - Becker, Werner
A1  - Dennerl, Konrad
A1  - Haberl, Frank
A1  - Lamer, Georg
A1  - Maitra, Chandreyee
A1  - Potekhin, Alexander Y.
A1  - Ramos-Ceja, Miriam E.
A1  - Santangelo, Andrea
A1  - Traulsen, Iris
A1  - Werner, Klaus
T1  - Phase-resolved X-ray spectroscopy of PSR B0656+14 with SRG/eROSITA and XMM-Newton
JF  - Astronomy and astrophysics : an international weekly journal
N2  - We present a detailed spectroscopic and timing analysis of X-ray observations of the bright pulsar PSR B0656+14. The observations were obtained simultaneously with eROSITA and XMM-Newton during the calibration and performance verification phase of the Spektrum-Roentgen-Gamma mission (SRG). The analysis of the 100 ks deep observation of eROSITA is supported by archival observations of the source, including XMM-Newton, NuSTAR, and NICER. Using XMM-Newton and NICER, we first established an X-ray ephemeris for the time interval 2015 to 2020, which connects all X-ray observations in this period without cycle count alias and phase shifts. The mean eROSITA spectrum clearly reveals an absorption feature originating from the star at 570 eV with a Gaussian sigma of about 70 eV that was tentatively identified in a previous long XMM-Newton observation. A second previously discussed absorption feature occurs at 260-265 eV and is described here as an absorption edge. It could be of atmospheric or of instrumental origin. These absorption features are superposed on various emission components that are phenomenologically described here as the sum of hot (120 eV) and cold (65 eV) blackbody components, both of photospheric origin, and a power law with photon index Gamma = 2 from the magnetosphere. We created energy-dependent light curves and phase-resolved spectra with a high signal-to-noise ratio. The phase-resolved spectroscopy reveals that the Gaussian absorption line at 570 eV is clearly present throughout similar to 60% of the spin cycle, but it is otherwise undetected. Likewise, its parameters were found to be dependent on phase. The visibility of the line strength coincides in phase with the maximum flux of the hot blackbody. If the line originates from the stellar surface, it nevertheless likely originates from a different location than the hot polar cap. We also present three families of model atmospheres: a magnetized atmosphere, a condensed surface, and a mixed model. They were applied to the mean observed spectrum, whose continuum fit the observed data well. The atmosphere model, however, predicts distances that are too short. For the mixed model, the Gaussian absorption may be interpreted as proton cyclotron absorption in a field as high as 10(14) G, which is significantly higher than the field derived from the moderate observed spin-down.
KW  - stars: neutron
KW  - X-rays: stars
KW  - pulsars: individual: PSR B0656+14
Y1  - 2022
U6  - https://doi.org/10.1051/0004-6361/202141105
SN  - 0004-6361
SN  - 1432-0746
VL  - 661
PB  - EDP Sciences
CY  - Les Ulis
ER  -