Estradiol administration modulates neural emotion regulation
1Department of Psychiatry and Psychotherapy, Innovative Neuroimaging, University of Tübingen, Tübingen, Germany; 2Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany; 3Institute of Psychology, University of Innsbruck, Innsbruck, Austria; 4Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 5Department of Psychiatry and Psychotherapy, University of Jena, Jena, Germany; 6Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden; 7Lead Graduate School, University of Tübingen, Tübingen, Germany
Variations of sex hormones during the menstrual cycle can lead to changes in emotion processing. The ability to successfully regulate one’s emotions is associated with better social abilities and mental health. While women show better performance in fear extinction learning under high estradiol (E2) compared to women under low E2 levels, little is known about the effect of E2 on emotion regulation. We explored whether E2 modulates emotion regulation in a functional magnetic resonance imaging paradigm and administered E2 valerate and placebo to 32 young naturally cycling women during their early follicular phase in a double-blind, within-subject, repeated-measures design. This standardized experimental control allowed us to explore the specific effect of E2 on emotion regulation while controlling for other hormones varying throughout the menstrual cycle. On the behavioral level, women reported less negative affect in the E2 condition. On the neural level, E2 administration was associated with lower activation in the right lingual- and left calcarine gyrus, right orbitofrontal cortex and left hippocampus relative to placebo. With respect to the main effect of down-regulation higher activation of the right superior frontal gyrus and left dorsomedial prefrontal cortex was seen. An interaction between drug condition and emotion regulation appeared for the left inferior frontal gyrus extending into the middle frontal gyrus indicating lower activation during down-regulation in the E2 condition than the placebo condition. The results fit well to a previously described psychoneuroendocrinological model in which E2 plays an important modulatory role in emotion regulation and thereby impacts mental health.
The modulation of social behavior in oral contraceptive users and naturally cycling women
1Universität Trier, Deutschland; 2Universität Konstanz, Deutschland
Oral contraceptives (OC) and sex hormones in naturally cycling women (NC) are related to a wide range of psychological variables eg, cognition and affect. With respect to social behavior, research is scarce. A first study from our lab documented a trend towards more prosocial behavior in NC compared to OC users but the underlying neuroendocrine mechanisms are still unknown. Potential candidates may be the sex hormones progesterone and estradiol. The present study investigated differences in social behavior in NC and OC users and measured estradiol and progesterone levels.
We used a paradigm adapted from behavioral economics as well as the Social Value Orientation (SVO) to assess prosocial and antisocial behavior and nonsocial risk behavior in 83 healthy women (38 OC users and 45 NC). In addition, we measured empathy (MET) and collected saliva samples to measure the basal levels of the hormones estradiol and progesterone.
Our analyses revealed higher levels of prosocial behavior in NC compared to OC users. This is validated by the SVO angle and type where NC showed a broader angle and are more often categorized as prosocial type than OC users. Moreover, NC showed more emotional empathy. Progesterone and trust were negatively correlated on a trend level, while progesterone was higher in NC than OC users. Our findings document a modulation of social behavior by OC that might be modulated by the sex hormone progesterone. Further research is needed to replicate our findings and extend them to other social behaviors.
Choosing right from wrong: Association of moral judgements with oral contraceptive use, testosterone, and the CAG repeat polymorphism in the androgen receptor gene
1TU Chemnitz, Deutschland; 2TU Dresden, Deutschland; 3Universität Würzburg, Deutschland
Differences in moral judgements are associated with various factors, including biological parameters. Previous studies have—albeit inconsistently—reported a stronger tendency towards utilitarian judgements in men. Utilitarian judgements are situation-dependent, outcome-based, and favor the ‘greater good’. In contrast, deontological judgements are based on situation-independent moral norms and principles of right and wrong. Available findings support the assumption of a connection between testosterone and utilitarian tendencies, particularly in women. We investigated differences in decisions in moral dilemmas between men, free cycling women, and women using combined oral contraceptives (COC) in a sample of N = 157. The used dilemma set allowed in addition to the traditional moral score the independent estimation of underlying deontological and utilitarian tendencies (cf. Conway & Gawronski, 2013). Significant effects of sex (p = .009) and endocrine status (p = .011) on utilitarianism were found with the highest levels in men and the lowest in free cycling women while COC users fell in between. Salivary testosterone correlated with utilitarianism in free cycling women (r = .303) and with reduced deontology in men (r = -.263). Furthermore, there was an interaction effect between endocrine status and the functional CAG repeat polymorphism in the androgen receptor gene in women (p = .001). COC users who carried two short alleles had reduced levels of deontology compared to carriers of long alleles. The findings underscore the role of androgens in moral judgements but also point to specific associations depending on sex and oral contraceptive use.
Within-person changes in cardiac vagal activity across the menstrual cycle: Implications for female health and future studies
1Heidelberg University Hospital, Germany; 2University of Illinois at Chicago, USA; 3Ulm University Medical Center, Germany
Interest in cardiac vagal activity (CVA; e.g., parasympathetically-mediated heart rate variability) as a biomarker of physical and mental health has increased exponentially; however, the association between the menstrual cycle and CVA remains unclear. In a first step, we therefore conducted a meta-analysis of 37 within-person studies on CVA change across different menstrual cycle phases in a total of 1004 naturally-cycling females (study 1). The meta-analysis revealed a significant CVA decrease from the follicular to the luteal cycle phase (d=−0.39, 95% CI [−0.67, −0.11]). As these cycle phase comparisons do not answer the question which of the ovarian hormones is primarily associated with CVA changes, we conducted two studies with repeated measures of CVA and salivary estradiol (E2) and progesterone (P4) in naturally-cycling females (study 2: N=40; study 3: N=50) to investigate hormonal mechanisms. Both study 2 and study 3 revealed that only P4 and not E2 was correlated with CVA, such that higher-than-usual P4 significantly predicted lower-than-usual CVA within a given woman. In conclusion, we found compelling meta-analytic evidence for a significant decrease in CVA from the follicular to the luteal cycle phase. In line with this, two follow-up studies suggest that these CVA fluctuations are mainly associated with P4. Future female health studies should investigate individual differences in these effects and potential consequences of cyclical CVA changes on daily functioning. Future studies involving CVA should control for cycle phase.
Adolescent oral contraceptive use and future major depressive disorder
1Leibniz Institut für Wissensmedien, Deutschland; 2University of British Columbia; 3University of Groningen; 4University Medical Center Leiden
Because of the widespread use of oral contraceptives (OCs) and the devastating effects of depression both on an individual and a societal level, it is crucial to understand the nature of the previously reported relationship between OC use and depression risk. Insight into the impact of analytical choices on the association may help to reconcile previous conflicting findings. For the present study, we tested in a specification curve analysis whether adolescent OC use was associated with a higher likelihood to experience an episode of major depressive disorder (MDD) in early adulthood in a 12-year prospective study among young women aged 13 years at baseline (N = 725). Across 818 models, overall, there was a significant association of adolescent OC use and MDD in early adulthood (median odds ratio [OR] median = 1.41; ORmin = 1.08; ORmax = 2.18, p < .001), which was primarily driven by the group of young women with no prior history of MDD (ORmedian=1.72; ORmin=1.21; ORmax=2.18, p < .001). Understanding the potential side effects of OCs will help women and their doctors make informed choices when deciding among possible methods of birth control.