Poster No:
783
Submission Type:
Abstract Submission
Authors:
Ann-Christin Kimmig1, Patrick Friedrich2, Bernhard Drotleff3, Michael Lämmerhofer3, Inger Sundström Poromaa4, Susanne Weis2, Birgit Derntl1
Institutions:
1Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany, 2Institute of Neuroscience and Medicine (INM-7), Research Centre Jülich, Jülich, Germany, 3Institute of Pharmaceutical Sciences, University of Tübingen, Tübingen, Germany, 4Department of Women’s and Children’s Health, University of Uppsala, Uppsala, Sweden
First Author:
Ann-Christin Kimmig
Department of Psychiatry and Psychotherapy, University of Tübingen
Tübingen, Germany
Co-Author(s):
Patrick Friedrich
Institute of Neuroscience and Medicine (INM-7), Research Centre Jülich
Jülich, Germany
Bernhard Drotleff
Institute of Pharmaceutical Sciences, University of Tübingen
Tübingen, Germany
Michael Lämmerhofer
Institute of Pharmaceutical Sciences, University of Tübingen
Tübingen, Germany
Susanne Weis
Institute of Neuroscience and Medicine (INM-7), Research Centre Jülich
Jülich, Germany
Birgit Derntl
Department of Psychiatry and Psychotherapy, University of Tübingen
Tübingen, Germany
Introduction:
The use of oral contraceptives (OC) has been associated with changes in functional brain architecture and socio-affective processes, specifically mood, with potential implications for mental well-being. OC-related depressive side-effects are expected to occur in a small subsample of hormone-susceptible OC users[1]. Nevertheless, flattening of positive mood was associated with the initiation of OCs in a longitudinal study[2]. Moreover, a recent placebo-controlled trial showed that OC use was linked to changes in functional brain connectivity, which were consistently associated with the OC-related emergence of adverse mood side-effects[3]. It has been suggested that OC intake could induce a hyper-progestogenic functional brain state[4]. However, previous studies have often been constrained by cross-sectional designs or failed to account for synthetic sex hormone concentrations. The aim of this study is to explore in a longitudinal design the association of changing hormone profiles with functional brain architecture in healthy young women and mood-related measures.
Methods:
To this end, we conducted two fMRI scans on 88 young healthy women, with an interval of three to eight months between scans. The participants were categorized into four groups: 26 natural cycling women during menses, 26 long-term OC users in the active intake phase, 25 OC discontinuers, and 11 OC starters before and after discontinuation or initiation, respectively. We collected 3T anatomical (MP2Rage) and resting-state data, along with blood hormone samples and self-reported mood measures (including Beck's Depression Inventory and the Positive and Negative Affect Schedule). The resting-state and anatomical data underwent pre-processing with fMRIPrep, which included slice time correction and normalization to the MNI152Lin6Asym template. For the analysis of parcel-wise resting-state activity, BOLD timeseries were extracted from the 268 nodes of the Shen atlas, and a noise correction for white matter and cerebrospinal fluid was applied. The first eigenvariate of the activity time course per node was then computed. Pairwise Pearson correlations were calculated for each node with all other nodes and standardized. In addition to mean-based analyses of changes in hormone concentrations and mood-related measures, we employed inter-subject representational similarity analyses (IS-RSA) to explore relationships between interindividual variability across different measurement levels, including changes of hormone concentrations, resting-state functional connectivity (RSFC), and mood-related measures.
Results:
Changes of RSFC in frontal, subcortical and cerebellar regions resembled the change patterns in progestogen levels (progesterone and progestin). Particularly noteworthy were the RSFC change patterns observed for the superior orbitofrontal gyrus (sOFG), which also corresponded with the change patterns of positive mood. Women who had more similar changes in progestogen concentrations, therefore, were also more similar regarding changes in sOFG RSFC and positive mood. Despite finding no correlation in the change patterns of depressive symptoms or negative affect with sex hormones or RSFC, the mean for depressive symptoms significantly decreased following the discontinuation of OCs.
Conclusions:
In conclusion, changes in functional brain architecture and positive mood seem to be associated with shifts in progestogen profiles rather than estrogen concentrations, posing the sOFG as a possible neural correlate of OC-related changes in positive mood. Additionally, our findings support the notion that women who encounter adverse mood effects are more likely to stop using OCs, potentially contributing to their underrepresentation in research studies and causing an underestimation of the number of women dealing with mental health issues related to OC use.
We thank the DFG, the German Academic Scholarship Foundation and the G.-A.-Lienert foundation for their financial support.
Emotion, Motivation and Social Neuroscience:
Self Processes 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Keywords:
Other - fMRI; sex hormones; oral contraceptives; mood; resting-state connectivity
1|2Indicates the priority used for review
Provide references using author date format
[1] De Wit, A. E. (2021), 'Hormonal contraceptive use and depressive symptoms: systematic review and network meta-analysis of randomised trials', BJPsych Open, vol. 7, no. 4, e110
[2] Lisofsky, N. (2016). 'Hormonal contraceptive use is associated with neural and affective changes in healthy young women', NeuroImage, vol. 134, pp. 597-606
[3] Hidalgo-Lopez, E. (2023). 'Triple network model of brain connectivity changes related to adverse mood effects in an oral contraceptive placebo-controlled trial', Translational Psychiatry, vol. 13, no. 209
[4] Casto, K. (2022), 'Hormone-based models for comparing menstrual cycle and hormonal contraceptive effects on human resting-state functional connectivity', Frontiers of Neuroendocrinology, vol. 67, 101036