Maria Umlauft

Alterations of hair cortisol and dehydroepiandrosterone in mother-infant-dyads with maternal childhood maltreatment

BackgroundChild maltreatment (CM) has severe effects on psychological and physical health. The hypothalamic-pituitary-adrenal (HPA) axis, the major stress system of the body, is dysregulated after CM. The analysis of cortisol and dehydroepiandrosterone (DHEA) in scalp hair presents a new and promising methodological approach to assess chronic HPA axis activity. This study investigated the effects of CM on HPA axis activity in the last trimester of pregnancy by measuring the two important signaling molecules, cortisol and DHEA in hair, shortly after parturition. In addition, we explored potential effects of maternal CM on her offspring’s endocrine milieu during pregnancy by measuring cortisol and DHEA in newborns’ hair.MethodsCM was assessed with the Childhood Trauma Questionnaire (CTQ). Cortisol and DHEA were measured in hair samples of 94 mothers and 30 newborns, collected within six days after delivery. Associations of maternal CM on her own and her newborn’s cortisol as well as DHEA concentrations in hair were analyzed with heteroscedastic regression models.ResultsHigher CM was associated with significantly higher DHEA levels, but not cortisol concentrations in maternal hair. Moreover, maternal CM was positively, but only as a non-significant trend, associated with higher DHEA levels in the newborns’ hair.ConclusionsResults suggest that the steroid milieu of the mother, at least on the level of DHEA, is altered after CM, possibly leading to non-genomic transgenerational effects on the developing fetus in utero. Indeed, we observed on an explorative level first hints that the endocrine milieu for the developing child might be altered in CM mothers. These results need extension and replication in future studies. The measurement of hair steroids in mothers and their newborns is promising, but more research is needed to better understand the effects of a maternal history of CM on the developing fetus.

Childhood maltreatment, postnatal distress and the protective role of social support

The postpartum period is a vulnerable period for women with a history of childhood maltreatment. This study investigated the association between childhood maltreatment and postnatal distress three months postpartum and examined the role of social support provided by different sources (intimate partner, parents, parents-in-law, and friends). Analyses are based on N=66 women, who were screened for maltreatment experiences shortly after parturition with the Childhood Trauma Questionnaire. Their levels of postnatal distress (symptoms of depression, anxiety, and stress; assessed with the Hospital Anxiety and Depression Scale and the 4-Item version of the Perceived Stress Scale) and postpartum social support (measured with the Postpartum Social Support Questionnaire) were assessed three months postpartum. Adjusting for educational level and the experience of a recent stressful event, childhood maltreatment was directly associated with higher levels of postnatal distress. Social support provided by friends moderated this association in a heteroscedastic regression analysis. No moderating effect was observed for support provided by the own parents, the intimate partner, or parents-in-law. The association between childhood maltreatment and postnatal distress was not mediated by social support. Additional analyses revealed no main, moderating, or mediating effects of satisfaction with support. Results suggest that support provided by friends may promote resilience during the postpartum period in women with a history of childhood maltreatment. Efforts to better understand the role of postpartum support and mechanisms that may enhance a mothers ability to develop and maintain supportive friendships may be promising for guiding preventive interventions.

Rank‐based permutation approaches for non‐parametric factorial designs

Inference methods for null hypotheses formulated in terms of distribution functions in general non-parametric factorial designs are studied. The methods can be applied to continuous, ordinal or even ordered categorical data in a unified way, and are based only on ranks. In this set-up Wald-type statistics and ANOVA-type statistics are the current state of the art. The first method is asymptotically exact but a rather liberal statistical testing procedure for small to moderate sample size, while the latter is only an approximation which does not possess the correct asymptotic α level under the null. To bridge these gaps, a novel permutation approach is proposed which can be seen as a flexible generalization of the Kruskal-Wallis test to all kinds of factorial designs with independent observations. It is proven that the permutation principle is asymptotically correct while keeping its finite exactness property when data are exchangeable. The results of extensive simulation studies foster these theoretical findings. A real data set exemplifies its applicability.

Intergenerational gene × environment interaction of FKBP5 and childhood maltreatment on hair steroids

BACKGROUND The inconsistency in results of cortisol alterations after childhood maltreatment (CM) might arise due to the fact that no study so far considered the effects of environmental factors such as maltreatment load and genetic factors such as the influence of FKBP5 genotype on stress hormone regulation. This study analyzed the interaction between the single nucleotide polymorphism rs1360780 within the FKBP5 gene and the severity of maternal CM experiences (maltreatment load) on hair steroid levels of mother-infant-dyads. METHODS Hair samples of N = 474 mothers and N = 331 newborns were collected < 1 week after parturition enabling a retrospective assessment of cortisol, cortisone, and dehydroepiandrosterone (DHEA) using mass spectrometry. The sum score of the Childhood Trauma Questionnaire operationalized the maternal maltreatment load. DNA from whole blood or buccal cells was used for FKBP5 genotyping. RESULTS The higher the maltreatment load, the higher maternal hair cortisol and cortisone levels in T allele carriers of FKBP5 rs1360780 were observed. Hair cortisol and DHEA levels of newborns with the T allele were reduced with an increasing maternal maltreatment load, while there was an increase of hair cortisol and DHEA in newborns homozygous for the C allele. CONCLUSIONS This study is the very first uncovering a gene (FKBP5) × environment (maltreatment load) interaction on hair steroids in mothers and their offspring, indicating an intergenerational transmission of hypothalamic-pituitary-adrenal axis alterations. These results may help to explain the inconsistency in previous findings on steroid hormone alterations after chronic and traumatic stress and should be considered in future studies.

Altered hair endocannabinoid levels in mothers with childhood maltreatment and their newborns

The endocannabinoid (EC) system possesses anti-inflammatory properties and seems to be altered in trauma-exposed individuals. In an intergenerational approach, this study investigated the link between childhood maltreatment (CM) experiences and alterations in the EC system. Hair samples of N = 142 mothers and N = 91 newborns were analyzed, retrospectively assessing EC regulation during the last trimester of pregnancy with four ECs: 1-arachidonoylglycerol (1-AG), N-oleoylethanolamide (OEA), N-stearoylethanolamide (SEA), and N-palmitoylethanolamide (PEA). Compared to mothers without CM, hair of mothers with CM showed significantly higher levels of 1-AG and lower levels of SEA. Newborns of mothers with CM exhibited higher levels of 1-AG and OEA. Furthermore, the higher the severity of maternal CM, the lower were maternal SEA levels and the higher neonatal OEA levels. Findings indicate altered EC levels during the last trimester of pregnancy in mothers with CM and their developing fetus, highlighting potential intergenerational effects from one generation to the other.

Diabetes mellitus and its effects on all-cause mortality after radiopeptide therapy for neuroendocrine tumors

We aimed to assess the risk of developing diabetes mellitus and its effects on all-cause mortality after radiopeptide therapy for neuroendocrine tumors (NETs). Methods: NET patients received somatostatin radiopeptide therapy with 90Y-DOTATOC or 177Lu-DOTATOC. The incidence of diabetes mellitus and its mortality were assessed using univariate and multivariate regression. Results: Overall, 1,535 NET patients were enrolled and received 3,807 treatment cycles. After treatment, 72 patients developed diabetes mellitus, including 47 cases after 90Y-DOTATOC and 25 cases after combined treatment. The diabetes mellitus risk was higher before than after DOTATOC (estimate, 0.0032; P < 0.001), and overall survival was similar in patients with and without diabetes mellitus (hazard ratio, 1.13; 95% confidence interval, 0.91–1.39; n = 1,535; P = 0.27). Conclusion: Radiopeptide therapy does not appear to increase the risk of developing diabetes mellitus in NET patients, whereas diabetes mellitus does not appear to increase the mortality of NET patients undergoing receptor-targeted radiopeptide therapy.

Resampling-Based Inference Methods for Comparing Two Coefficients Alpha

The two-sample problem for Cronbach’s coefficient

Wild Bootstrapping Rank-Based Procedures: Multiple Testing in Nonparametric Split-Plot Designs

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