Neuroendocrine changes during hormonal transition phases are associated with an increased risk for mental disorders. Stress reactivity and sensitivity to stressful stimuli are also influenced by these neuroendocrine shifts and are therefore altered during such phases. Epigenetic mechanisms play a key role in regulating hormonal changes and mediating their impact on behavior, including the development of mental health conditions.

The current project aims to investigate the epigenetic regulation of relevant genes and their association with stress reactivity during puberty, and to compare these findings with changes observed during menopause. We will study pre- and post-pubertal girls as well as pre- and postmenopausal women. In addition, a longitudinal sub-cohort of girls and women already enrolled in the study will be followed over time to explore epigenetic alterations and shifts in stress reactivity in more detail across hormonal transition periods.

A central goal of the project is to examine whether genes identified as epigenetically altered during puberty also undergo similar changes during menopause. This will help determine whether different hormonal transition phases are characterized by shared epigenetic signatures. Furthermore, we will analyze how these epigenetic modifications affect gene expression profiles and correlate the findings with stress response data available in a subset of participants.

Stress reactivity will be assessed through cortisol profiling as well as through behavioral and neural responses to a standardized stress paradigm during fMRI (MIST). During the research stay in Uppsala, the results obtained from healthy women will be compared to those from women diagnosed with PMDD (premenstrual dysphoric disorder).

Keywords: Puberty, Menopause, Epigenetics, Stress

This project is part of the research group „Molecular Psychiatry“. Find more Information here: Molecular Psychiatry

In this project we want to test a model on the association between estradiol (E2), stress and major depressive disorder (MDD) which was proposed by Albert and Newhouse (2019). The authors suggested that E2 may alter brain systems that interface with stress-related processes in MDD. Furthermore, the model assumes that reproductive events potentially change the mechanisms underlying these associations between E2 and stress-related processes. After menopause, E2-administration led to higher subjective stress after an acute stress induction in females without a history of MDD. The pattern was reversed in females with a history of MDD. So far, an exploration of changes in brain activity and a comparison to pre-menopausal females is missing.  Therefore, in this project we will extend project P02 from the first IRTG-cohort and assess the association of E2 administration in pre- and post-menopausal females with MDD. Additionally, control groups (pre- and post-menopausal females without MDD) will be included. Data for the control groups will partially be derived from project P02 of the first IRTG-cohort. To match groups for specific variables, it might be necessary to still assess healthy pre- or post-menopausal females and fill up the control groups.  Information on the association between E2 and stress reaction, how this interacts with a diagnosis of depression, and whether this changes with reproductive status is missing. Exploring the impact of E2 on brain health before and after menopause is necessary to extend our knowledge on females mental health, and to further stimulate the development of subjective interventions.

Keywords: Natural Cycle vs. Post-Menopausal, Major Depressive Disorder

This project is part of the research group „Women’s Mental Health and Brain Function“. Find more information here: Women´s Mental Health and Brain Function

Hormonal contraception (HC) is used by millions of women, and oral contraceptives are the most frequently prescribed pill worldwide (United Nations 2019). Since side effects, such as depressive symptoms, are typically reported as the main reason for discontinuing HC use, additional research into stress-related mechanisms as potential side-effects of HCs is crucial.  Our overarching aim is to evaluate the effects of HC use on mood homeostasis and stress reactivity to identify risk markers for the onset of depressive episodes during HC use. In funding period (FP) 1, we have assessed changes in brain responses and functional connectivity during acute psychosocial stress (Aim 1), early changes in mood and well-being using ambulatory assessment (Aim 2), and mid-term changes in trait-like psychopathology dimensions (Aim 3) as individual risk markers. In FP2, we are planning to extend this approach to additional groups of women starting the use of the progestogen-only „mini pill“ as well as long-term users. By extending the previously established work program to additional HCs, the next project will be able integrate the results of FP1 to contrast the effects of different HCs on stress reactivity and mental health.  We anticipate that building on the empirical foundation provided by FP1 will strengthen the overall contribution of the project to the translational goals of the work. The extended project will help us address more nuanced mechanistic answers, such as if changes in stress reactivity are driven by estrogen and/or progestin, providing a much-needed advance in the understanding of HC-induced psychological side-effects.  

This project is part of the Henes Lab. Find more information here: Prof. Dr. Melanie Henes

Millions of girls and women worldwide experience menstrual cycle-related mood disturbances, including affective lability, irritability, depressed mood, and anxiety. These symptoms define premenstrual syndrome (PMS, affecting 20-30% of women) and its more severe form, premenstrual dysphoric disorder (PMDD, affecting 3-8% of women). Despite their high prevalence and significant impact on mental health, the underlying neural mechanisms remain poorly characterized, and treatment options are limited. Altered stress reactivity is a core feature of depressive disorders, including major depressive disorder (MDD). Neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (dlPFC) have shown promise in modulating stress-related neural circuits and alleviating depressive symptoms in MDD.  This project investigates the neural correlates of stress reactivity (using previously acquired IRTG data) and the modulatory effects of rTMS in individuals with PMS/PMDD compared to those with MDD. Two demographically matched female cohorts will be enrolled: one meeting established criteria for moderate to severe PMS or PMDD, and one diagnosed with MDD. Each participant will complete two experimental sessions, receiving either real or sham rTMS of the dlPFC in a randomized, within-subject crossover design. rTMS will be applied prior to a stress-induction paradigm during functional MRI (fMRI) scanning to assess modulation of stress-responsive brain activity. To capture symptom dynamics across time, daily tracking of mood and depressive symptoms will be implemented throughout the study period. Symptom severity will be will be incorporated as a continuous moderator to evaluate its association with both baseline neural reactivity and the efficacy of rTMS-induced neuromodulation, facilitating insights into individual variability in treatment response.  This interdisciplinary project combines neuroimaging, clinical assessment, and non-invasive brain stimulation to explore shared and distinct mechanisms across hormone-sensitive and non-hormone-sensitive depressive syndromes/disorders. It offers training in advanced fMRI, neuromodulation techniques, and female neuroendocrinology – suitable for a candidate with a strong interest in women’s health, clinical neuroscience and affective disorders. Offering valuable cross-institutional mentorship and research exposure, this project will be co-supervised by Prof. Erika Comasco, an expert in PMDD neural correlates at the University of Uppsala.

Keywords: PMDD/MDD, TMS, Stress

This project is part of the research group „Psychophysiology and Optical Imaging“. Find more information here: Psychophysiology and Optical Imaging

Our overarching aim is to evaluate the effects of hormonal transition phases on energy and mood homeostasis to better understand whether aberrant dopamine signaling contributes to key motivational symptoms such as anhedonia or changes in appetite. To this end, in the first funding period (FP), we have assessed differences in resting energy expenditure and blood levels of circulating hormones (Aim 1), longitudinal changes in mood (Aim 2), as well as neurobehavioral changes after administration of a dopamine precursor (Aim 3). To provide a good reference for hormonal transition phases, we focused on naturally cycling women and two representative phases with marked differences in hormone levels. For FP2, it would be highly relevant to extend this work to a group of perimenopausal women as well as an age-matched control group of men. This combination would allow us to quantify the association of hormonal transition phases with behavioral consequences (e.g., mood swings, anhedonia) while contextualizing it with the data provided by FP1. In addition, it would be beneficial to strengthen the longitudinal EMA/hormone analysis part to capture this transition phase for future translational efforts.    Hence, the proposed extension would provide crucial insights into a potential modulatory mechanism that may link hormonal transition phases to a wide range of metabolic and motivational symptoms, which could provide an avenue for future interventions.

This project is part of the „neuroMADLAB“. Find more information here: neuroMADLAB

The hypothalamic neuropeptide oxytocin not only regulates reproductive and psychosocial function but also contributes to metabolic control and reward processing. We have shown that the acute administration of oxytocin inhibits reward-driven food intake in men while dampening stress axis activity. It is also known that endogenous oxytocin concentrations peak around ovulation and are positively associated with BMI in women; eating disorders – hallmarks of impaired mental health in women – imply dysfunctional oxytocin signaling. However, although sex steroids are relevant regulators of the oxytocin system, the contribution of oxytocin to reward processing in females has not been systematically assessed. Against this background, we want to investigate the role of oxytocin in the processing of rewards in females in dependence of their metabolic status, of sex steroids, and of peri- and post-menopause.

This project will be part of the Hallschmid lab. Find more information here: Hallschmid Lab

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age and is associated with a wide range of reproductive, endocrine, metabolic, cardiovascular, and mental health outcomes. These outcomes are thought to be influenced by central mechanisms, which may play a key role in the pathogenesis of PCOS. One potential mechanism involves the effects of androgens.

Recent neuroimaging findings suggest altered brain structure and function in women with PCOS, particularly in regions involved in reward processing and emotion regulation. In this study, we aim to investigate the processing of both primary and secondary rewards in women diagnosed with PCOS, and to compare these findings with those from naturally cycling women, with and without androgen administration. The expected results will contribute to a better understanding of the pathophysiology of PCOS and clarify the role of hyperandrogenism in shaping reward-related brain networks.

Keywords: PCOS, Naturally Cycling, Androgen

This project is part of the research group „Women’s Mental Health and Brain Function“. Find more information here: Women´s Mental Health and Brain Function

Breast cancer, the most common cancer among women, impacts not only physical health but also mental well-being and overall quality of life. Anti-estrogen therapy, a standard treatment for hormone receptor-positive breast cancer, can influence both body and mind. However, little is known about its effects on the brain, or whether these effects differ between premenopausal and postmenopausal women.

This study aims to systematically examine the impact of anti-estrogen therapy on brain structure, reward processing, sexual function, mental health, and quality of life in women diagnosed with breast cancer, with a particular focus on differences between pre- and postmenopausal patients. In addition to women undergoing anti-estrogen therapy, the study will include age-matched women with hormone receptor-negative breast cancer and healthy controls.

To our knowledge, this is the first study to investigate the immediate effects of anti-estrogen therapy on brain architecture. It will provide novel insights into the short- and medium-term impact of such treatment on women’s mental and physical health.

This project is part of the research group „Women’s Mental Health and Brain Function“. Find more information here: Women´s Mental Health and Brain Function

Background: Social networks are part of the daily lives of most adolescents. The use of social networks can improve, impair or leave adolescents‘ well-being unaffected. Known factors in this context are the cognitive tendency to social comparison, the duration of use and internalizing psychopathological symptoms. At the same time, the hormonal situation in the female cycle influences how situations are evaluated cognitively and emotionally. It is unclear what influence the female cycle has on cognitive and affective processes when using social networks, what role the duration of use and the age of first use play and what influence symptoms of mental illness have in this context. Objective and research question: This study aims to identify further risk and protective factors and contribute to the protection of girls and young women using social networks in the future. The aim is to investigate whether the duration and frequency of use, the tendency to social comparison, psychological well-being, body satisfaction and affect change systematically directly after the use of social networks during the female menstrual cycle. Furthermore, it will be examined whether the age of first use of social networks and the duration of use are associated with differences in the brain. We will also investigate whether psychopathological symptoms have an influence on these correlations. Methods: Young girls aged 13 – 21 years who do not use hormonal contraception will be examined for one cycle using smartphone tracking, prompted surveys directly after social media use and daily surveys in the evening (EMA). In addition, a baseline survey is conducted at the beginning of the study. Furthermore, the participants are invited to an fMRI measurement and blood sample.

Keywords: Adolescence, Social Networks, Natural Cycle

This project is part of the research group „Internet Use Disorder“. Find more information here: Internet Use Disorder

There is growing evidence that the fetus in utero is able to perceive auditory and visual stimuli with social relevance, e.g. maternal voice and face like stimuli. However there is a knowledge gap, whether this is affected by the emotional status of the mother. The hypothesis is that the detection of social stimuli is attenuated in women with high emotional stress. In the proposed study we aim to recruit pregnant women and investigate fetal brain and heart responses to maternal voice and face like stimuli. The women will be recruited to cover a large scale of different levels of chronic stress, assessed by questionnaires. The maternal voice will be pre-recorded. Afterwards the auditory stimuli will be either presented in its original form or scrambled. The study will include a mismatch like protocol. In a second study we will investigate visual face like stimuli and random dot patterns to determine the fetal reaction to these stimuli again in a mismatch paradigm. The recordings will be performed at 28 and 34 weeks and during the first four weeks after birth.

This project will be part of the „Preissl Lab“. Find more information here: Preissl Lab

This PhD thesis will contribute to a better understanding of the moderating influence of changing societal gender norms, own gender identities and biopsychological predispositions on women’s (and men’s) mental health trajectories across stressful life course transitions, such as (unintended) parenthood, changes in contraception, and divorce. The empirical analysis will draw on representative large-scale panel data studies from Germany. The first part of the project will extend existing cross-sectional or longitudinal country comparisons on the gender equality paradox in mental health, which have suggested that women report higher levels of depressive symptoms across time and geographic regions (Kaiser et al., 2025) and possibly more so in countries or periods with more gender-equal political institutions and norms (Campbell et al., 2021; Guo et al., 2024; Herlitz et al., 2024). For a more detailed understanding of these time trends and possible causal mechanisms, we will conduct longitudinal analyses at the individual level to disentangle cohort, age and period effects based on longstanding representative household panel data from Germany between about 2000 to 2024. We will investigate more in detail specific life course stages, such as (unintended) parenthood, in which significant changes in the gender gaps take place, and whether their negative mental health consequences have reduced as parental leave and childcare institutions have become more supportive of gender equality over time. The second part of the project explores whether women who start using hormonal contraception report changes in depressive symptoms and sexual desire over time including moderator analyses to explore heterogeneities depending on previous depressive symptoms, personality, BMI, and age. To reduce the risks of unobserved heterogeneity or reverse causality, we apply fixed-effects models and instrumental variables in combination with statistical matching. The third part of the project will build on existing cross-sectional crossnationally comparative results of the first IRTG cohort which show that individuals with less polarized and more non-conforming gender identification report more frequent depressive symptoms, in particular in more traditional gender regimes. To move towards a more causal identification of these relationships, the project will explore how changes in mental health after transition to (unintended) parenthood and single or separated parenthood after divorce vary depending on individuals‘ gender identification and regional institutional support, such as childcare provision.

This project will be part of the Schober lab. Find more information here: Schober Lab

The project builds on our first cohort wave 1 methodological developments of machine learning models for brain sex classification. We will extend the current T1-based framework to other brain imaging modalities such as resting state functional MRI. As before, we will train, tune and validate robust machine learning models for brain sex classification in large, openly available cohorts and biobanks covering different age ranges from youth to old age. As in our ongoing development of limbic system specific models, we will develop network specific models for different brain functional network units. We will then apply these fMRI-based models to the full set of previously IRTG-collected data, creating fMRI based sex class probabilities for each individual and time point in the IRTG cohort. Next, we will explore to what degree these multivariate class probabilities act as a biomarker or proxy for different women’s brain health factors. We will investigate correlations with hormonal data across different sensitive phases and explore to what degree our markers relate to women’s health, gender and behavioral data. As a side product, this project offers standardized processing of IRTG fMRI and large cohort fMRI data, which can be shared with other IRTG projects for further use.

This project will be part of the Kaufmann lab. Find more information here: Kaufmann Lab