Duration February 2017 until January 2020

Stress is defined as a non-specific bodily response to any type of demand that exceeds previous coping capabilities. Numerous factors influencing the stress response have been identified so far, thus explaining individual stress vulnerability is a current challenge in stress research. It is already known that women and men react differently to stress: while men report more physiological reactions, women tend to describe subjective stress and negative affect. Although long demonstrated in animal studies, human studies to date leave open how this gender difference is modulated by external and internal factors.

A promising approach to investigate these differences is therefore the analysis of genetic and epigenetic parameters. Regarding stress, a polymorphism of the serotonin transporter (5-HTTLPR) has been associated with stress vulnerability. However, subsequent replication attempts have failed, possibly because this effect is moderated by complex interactions of sex, sex hormone concentration, and other genotypes. In addition, there is evidence that past traumatic experiences may lead to permanent structural and regulatory modulations and thus may also cause alterations in hypothalamic-pituitary-adrenocortical (HPA) axis function. The underlying biological mechanism is still unclear, but previous findings increasingly point to the role of epigenetic mechanisms that regulate gene expression and thus subsequently influence complex neuronal functions. One of these mechanisms is DNA methylation.

Therefore, the proposed project will investigate the subjective, psychophysiological and neural stress response of 165 women and 165 men genotyped for 5-HTTLPR using a psychosocial stress paradigm. The measurements will be performed at two sites (Aachen, Tübingen). The methylation level of the serotonin transporter gene (SCL6A4) will additionally be assessed in all subjects. Since the testosterone level may have a modulating influence on the stress reaction depending on the genotype, this effect will be examined in women and men. Neuropsychological and psychophysiological data will also be collected, which will be related to the results on stress response and cognitive abilities.

The question of the specificity of the stress response, taking into account gender, genotype and epigenetic parameters, may contribute essentially to our understanding of individual stress vulnerability and stress regulation processes. Since many psychiatric disorders are associated with stress, this also has important clinical implications. (Prof. Dr. Vanessa Nieratschker & Prof. Dr. Ute Habel, RWTH Aachen)

(DFG project with Prof. Dr. Ute Habel, RWTH Aachen)

Duration 2020-2022

Transgender persons do not identify with their biological sex and want to live and be accepted as a person of the opposite sex. They are often exposed to severe discrimination and have a higher risk of poorer mental and physical health. Many transgender individuals seek hormone treatment or gender reassignment surgery. A recently growing number of imaging studies have previously examined the structural and functional correlates of transgender, and found signs of feminization in some sexually dimorphic brain regions in transwomen, as well as corresponding signs of masculinization in transmen. Overall, the data remains limited. In addition, most studies have faced a number of methodological problems, including small samples and lack of control groups or comparisons between transwomen and transmen. The present project takes a longitudinal approach to quantify the effects of opposite-sex hormone therapy on brain and behavior by assessing brain structure and function over a six-month period after initiation of therapy. In addition to psychopathological ratings and questionnaires on stress, emotions, and subjective well-being as well as quality of life, we will measure behavior and neural correlates using paradigms to discriminate female and male voices and faces. Furthermore, we will test the hypothesis of a neurobiological gender continuum in the human brain that challenges the validity of a binary gender conceptualization. Based on functional connectivity and questionnaire data, we will use data-based machine learning algorithms to classify each person's gender identity regardless of their biological sex. We hope that such bio-behavioral markers of gender identity will advance clinically and socially relevant knowledge in the field of transgender research. (Carolin Lewis, Melina Grahlow)

Contact:

carolin.lewis@med.uni-tuebingen.de

melina.grahlow@med.uni-tuebingen.de

With the increasingly widespread use of hormonal contraceptives, it is important to understand their effects on the body and brain. While there have been a handful of studies on oral contraceptives (OC), they have mainly focused on the physical effects. A few studies have also shown effects on the brain, particularly stress reactivity, emotion regulation, and links to mental disorders. Studies on hormonal IUS (LNG-IUS) are even rarer. In our proposed study, we aim to investigate stress reactivity and how it can be altered by the use of hormonal contraceptives. A better understanding of the mechanisms of stress reactivity is of utmost importance to understand the occurrence of stress-related mental disorders such as depression and anxiety, especially in the context of hormonal contraception. Indeed, both endocrine systems - the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis - interact with each other. To date, only one study has examined the interaction of LNG-IUS and stress reactivity: While OC users tend to show a blunted cortisol response compared to naturally menstruating women, LNG-IUS users seem to show a potentiated response. We aim to examine stress reactivity in four groups of women - naturally menstruating women, established OC users and LNG-IUS users/starters - and how this may be altered by the use or initiation of hormonal over time. To carefully examine the effects of LNG-IUS and the stability of these over time, we will measure stress reactivity (subjective, hormonal, and behavioral) of all women multiple times. This will allow us to examine a) how the stress response is modulated by LNG-IUS onset and b) how individual stress responses evolve. As such, this project has enormous societal relevance, as women worldwide can make a more informed decision about which contraceptive method to choose.(Zoé Bürger)

Contact:

zoe.buerger@med.uni-tuebingen.de

When it comes to moral dilemmas, a moral dichotomy often exists for their resolution. The infamous trolley and bridge problems illustrate the conflict: if an out-of-control streetcar is heading toward five track workers on the track, both deontologists (rule-based morality) and utilitarians (outcome-based morality) would divert the trolley to a track with only one worker. But if a streetcar is approaching five track workers on the track, deontologists would forbid pushing a very large man onto the track to stop the car, while utilitarians would allow this action as morally permissible. Understanding how our moral decision making is processed in our brains during dilemmas is critical for both social and clinical reasons.

Neuroimaging studies have found that two distinct neural activation pathways contribute to the moral dichotomy: stronger activations in emotion-associated regions occur more often deontologically in response to dilemmas, whereas stronger activations in cognition-associated regions - utilitarian. Personal characteristics (e.g., empathy, prosociality, risk-taking) and gender also contribute to differences in the neurobiological realization of moral decision-making. In behavioral studies, utilitarian responses have been negatively associated with trait empathy and humanized sacrifice in dilemma scenarios and positively associated with psychopathy or deficits in empathy. Functional neuroimaging studies with children and adults have found that the sight of pain or emotional distress elicits a neural response in a network composed of regions involved in moral decision-making.

Within this study, we aim to elucidate the following: (i) gender differences in neural activation during moral decision making and their association with gender-specific performance, and the (ii) influence of personal characteristics on behavioral and neurobiological mechanisms of moral dilemmas in men and women.

The study will examine healthy men and women scanned in fMRI during two experimental paradigms measuring 1. moral sensitivity and 2. decision making. The results will allow us to draw conclusions about whether and how personal characteristics and gender influence the behavioral and neural correlates of moral decision making. (Aiste Ambrase, Melina Grahlow)

Contact:

aiste.ambrase@med.uni-tuebingen.de

melina.grahlow@med.uni-tuebingen.de

fortüne project

Duration 2018 - 2020

Every day we are confronted with numerous situations in which we are judged by others. Inappropriate handling of evaluations by others (e.g. with sentences like "You did that badly") are a central problem of many patients with mental disorders.
The aim of the study is to assess individual subjective, peripheral physiological and neural responses to social videos in order to adapt these videos for use in a clinical context. In addition, effects on functional connectivity in the brain will be recorded using functional magnetic resonance imaging (fMRI). The data will be used to further improve interventions for patients to deal with social judgement. (Lydia Kogler)

Contact:

lydia.kogler@med.uni-tuebingen.de

CIN EXC 307 Project with Prof. Dr. Martin Walter, Prof. Dr. Hubert Preissl, Prof. Dr. Ingeborg Krägeloh-Mann, Prof. Dr. Inger Sundström Poromaa, University of Uppsala, Prof. Dr. Lisa Ekselius, University of Uppsala, Prof. Dr. Fotis Papadopozlos and Prof. Dr. Alkistis Skalkidou, University of Uppsala

Duration 2017 - 2020

Pregnancy is one of the major hormonal upheaval phases in a woman's life, along with puberty and menopause. Additionally, it represents a critical developmental phase for the unborn child. Studies show that the origin of many structural changes in neuronal and psychological disorders can already be traced back to this early developmental phase. The immense increase in female sex hormones during pregnancy also causes changes in brain areas involved in emotional processes. Already natural hormonal fluctuations, especially of the female sex hormone estradiol, influence a successful handling of emotions and the underlying brain activity. In this context, estradiol can induce changes in mood, emotion processing, color perception and hearing. This has been demonstrated particularly in studies of the influence of the menstrual cycle. A better understanding of the factors that contribute to the improvement or deterioration of our ability to regulate emotions during pregnancy is important in order to better understand the adaptation of the brain as a result of pregnancy and, more fundamentally, the influence of sex hormones on our emotional abilities. This study will therefore investigate the influence of estradiol concentration on the ability to regulate emotions and the underlying brain activity. Subjects will undergo an emotion regulation paradigm in a magnetic resonance imaging (MRI) scanner. Three further subprojects will investigate maternal stress during pregnancy using fMEG, the predictors for the development of postpartum depression and the development of the child.(Elisa Rehbein, Ferdinand Sörensen)

Contact:

elisa.rehbein@med.uni-tuebingen.de

ferdinand.soerensen@med.uni-tuebingen.de

DFG project

Duration 2017 - 2021

Oral contraceptives (OC) are taken by millions of women worldwide every day. No other "pill" has had such a resounding effect on society, mainly because it has enabled women to prevent or control pregnancy and thereby critically challenged social conventions and gender stereotypes. While a large number of studies have demonstrated the influence of endogenous sex hormones on a wide range of human behaviour, little is known about the psychological and neurobiological effects of OC use. However, the few studies that do exist point to a significant change in women's social behavior that could also have far-reaching individual and societal consequences: for example, mate choice is altered by OC ingestion, and sexual desire, arousal, and reward processing are also affected. Sex hormone concentrations therefore have a major impact on important aspects of a woman's life. Whether OC intake also influences sexual appetence and related approach-avoidance behaviors is unknown.
Therefore, this research project is dedicated to investigate the influence of endogenous vs. synthetic sex hormone concentrations and OC intake on sexual appetence and the neural correlates. Three groups of women will be included: 1) naturally menstruating women, 2) women starting OC intake after the 1st measurement, and 3) women who have been taking OCs for at least 12 months. All participants will be screened twice at 3-month intervals. For this purpose, an approach-avoidance task will be performed in the MR scanner. Furthermore, functional connectivity during the resting-state as well as brain volumetry will be assessed on both measurement dates and the influence of OC intake as well as cycle- and pill-related sex hormone fluctuations on it will be analyzed.
The present project focuses on the combination and integration of behavioral, subjective, hormonal and neural parameters regarding social behavior in women. It is the first study to explicitly address the influence of OC intake on these different measures and parameters and thus to shed light on the possibility of characterizing the psychological and neurobiological implications of OC intake. (Ann-Christin Kimmig)

Contact:

ann-christin.kimmig@med.uni-tuebingen.de

DFG-Project with Prof. Dr. Vanessa Nieratschker & Prof. Dr. Ute Habel, RWTH Aachen University

Duration 2017-2021

Stress is defined as a non-specific bodily response to any kind of demand that exceeds previous coping capabilities. Numerous factors influencing the stress response have been identified so far, therefore explaining individual stress vulnerability is a current challenge in stress research. It is already known that women and men react differently to stress: while men report more physiological reactions, women tend to describe subjective stress and negative affect. Although long demonstrated in animal studies, human studies to date leave open how this gender difference is modulated by external and internal factors.
A promising approach to investigate these differences is therefore the analysis of genetic and epigenetic parameters. Regarding stress, a polymorphism of the serotonin transporter (5-HTTLPR) has been associated with stress vulnerability. However, subsequent replication attempts have failed, possibly because this effect is moderated by complex interactions of sex, sex hormone concentration, and other genotypes. In addition, there is evidence that past traumatic experiences may lead to permanent structural and regulatory modulations and thus may also cause alterations in hypothalamic-pituitary-adrenocortical (HPA) axis function. The underlying biological mechanism is still unclear, but previous findings increasingly point to the role of epigenetic mechanisms that regulate gene expression and thus subsequently influence complex neuronal functions. One of these mechanisms is DNA methylation.
Therefore, the proposed project will investigate the subjective, psychophysiological and neural stress response of 165 women and 165 men genotyped for 5-HTTLPR using a psychosocial stress paradigm. The measurements will be performed at two sites (Aachen, Tübingen). The methylation level of the serotonin transporter gene (SCL6A4) will additionally be assessed in all subjects. Since the testosterone level may have a modulating influence on the stress reaction depending on the genotype, this effect will be examined in women and men. Neuropsychological and psychophysiological data will also be collected, which will be related to the results on stress response and cognitive abilities.
The question of the specificity of the stress response, taking into account gender, genotype and epigenetic parameters, may contribute essentially to our understanding of individual stress vulnerability and stress regulation processes. Since many psychiatric disorders are associated with stress, this also has important clinical implications. (Hannes Noack)

Contact:

hannes.noack@med.uni-tuebingen.de

Duration January 2016 until December 2017

Visual attention processes are essential for interpersonal interaction. In this regard, gender and the female menstrual cycle are influential factors. Androstadienone, a socially-relevant human odorant, influences attentional processes by directing them towards emotional stimuli. However, the exact role of socially-relevant odorants in human interaction is poorly studied and the neurobiological basis of attentional modulation in women and men is unknown. Therefore, the present project aims to analyze the effect of androstadienone on selective attention and attentional biases and their neural bases in relation to gender and menstrual cycle phase. All participants will undergo two fMRI examinations (androstadienone vs. placebo). A significant modulation of both attentional processes by androstadienone is expected, with gender and cycle phase playing a crucial role. The modulation of emotional-cognitive processes by gender, menstrual phase or socially relevant odorants such as androstadienone has not yet been investigated sufficiently. In order to be able to subsequently work out derivations for gender-specific behaviour and prevalence rates (e.g. depression in women) as well as starting points for specific therapeutic interventions, there is a great need for the investigation of these effects.

Duration 2011 until 2015

Prof. Dr. Ewald Moser & Prof. Dr. Christian Windischberger, MUW Vienna, Prof. Dr. Ute Habel, RWTH Aachen, Prof. Dr. Ruben Gur, UPENN and Prof. Dr. Ilse Kryspin-Exner, UNI WIEN

Female or male - our gender is one of the most important biological factors of humans with far-reaching consequences for many aspects from social-emotional abilities to health. Especially the physiological and psychological reactions to stress have a major impact on human health and here previous studies suggest gender differences in subjective, physiological as well as neuronal correlates. Confronted with social stress, women show a reduced cortisol response but strong subjective affect and increased neural activation in limbic regions. Interestingly, during performance stress, men show reduced subjective distress but stronger physiological responses. Moreover, the stronger neuronal activation in prefrontal areas in men compared to women suggests a more regulatory response. Despite the behavioral evidence of sex differences in stress responses depending on the type of stressor, there is no imaging study that directly compares subjective, physiological, and neural responses to performance and social stress in women and men. Using functional high-field magnetic resonance imaging (fMRI), the aim of the study presented here is to examine sex differences in stress responses and their modulation by the type of stressor (performance vs. social stress). The use of a three-level approach (subjective, physiological, and neural) allows us to explore complex effects and interactions within a comprehensive stress model. The analysis of neural network models in addition to a purely localization-based approach in the analysis of fMRI data can provide important insights regarding stress-regulatory as well as gender-specific mechanisms. The neuronal regions of particular interest include cortical (e.g. prefrontal cortex) as well as subcortical areas (e.g. hippocampus and amygdala). On the physiological level, the effect of stress hormones as well as sex hormones on subjective and neuronal stress responses will be systematically investigated. The investigation of the mechanisms underlying gender-specific stress responses can contribute essentially to our understanding of prevalence differences in stress-related diseases, e.g. depression in women and cardiovascular diseases in men.