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Derntl, B.

Publications and source records attributed to Derntl, B..

15 recordsLinked to original sources

Menstrual cycle phase and premenstrual symptoms in relation with the stress response: an fMRI study

Objective: Women with premenstrual syndrome (PMS) experience affective lability, irritability, depressed mood, and anxiety during the late luteal phase of the menstrual cycle. Stress reactivity may contribute to the development of these symptoms, yet neural correlates remain unexplored. We examined neural, behavioral and endocrine stress responses across menstrual cycle phases in women with and without PMS. Methods: 26 women with PMS and 24 women without PMS participated in two fMRI sessions, during the mid-follicular (days 5 to 11) and late-luteal phases (days -7 to -1). Participants completed the Montreal Imaging Stress Task (MIST). Subjective stress ratings and salivary cortisol were collected at six time points before and after stress induction. Stress-related brain activation was assessed using whole-brain and region-of-interest analyses. Results: Subjective stress ratings increased as expected from before to after the MIST, with no group or phase differences. Salivary cortisol was significantly higher during the mid-follicular phase, with no group effect or significant pre-post MIST difference. While the stress task elicited activation patterns in stress-related regions, whole-brain analysis revealed no significant effects of group (PMS vs. no PMS) or menstrual cycle phase (follicular vs. luteal) on the neural stress response. Considering premenstrual symptom severity as a predictor revealed significant group-by-symptom severity interactions in the right inferior frontal gyrus and the right superior temporal gyrus. Conclusion: Using a within-subject repeated-measures design, we found neural responses to psychosocial stress to be stable across menstrual cycle phases. Individual differences in symptom severity may nevertheless be associated with differences in stress-related brain activation.

neuroscience↗

Sex-specific associations of estradiol and instrumental harm with moral decision-making

Previous research suggests that women and men may differ in moral decision-making involving instrumental harm. However, prior findings have yielded inconsistent explanations for these differences, suggesting effects of gender expression, empathy, action tendencies, and biological causes, such as differences in gonadal hormone levels. Yet, no data exists on the effects of endogenous estradiol and progesterone on moral decision-making, while the effects of testosterone are inconsistent. Our study aimed to close this research gap. A sample of 137 cis individuals (73 women, 64 men) completed a moral dilemma task based on the Consequences, Norms, Inaction (CNI) model either in the morning or evening. Relevant personality traits, including agreement with instrumental harm, impartial beneficence, empathy, and gender expression, were assessed via self-report. Blood samples were analyzed for estradiol, progesterone, testosterone, and cortisol. Contrary to prior literature, no behavioral differences between women and men were observed in moral decision-making. However, self-reported agreement with instrumental harm positively predicted sensitivity to consequences and negatively predicted adherence to moral norms in the whole sample. Estradiol concentration positively predicted sensitivity to consequences in the morning women group, and general inaction tendency in the morning men group. Overall, these findings highlight the joint influence of biological and personality factors on moral choices and hint towards subtle sex/gender differences.

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Brain anatomy in major hormonal transition phases: Longitudinal and cross-sectional volume associations with menarche and menopause

BackgroundHormonal transition phases represent windows of increased neuroplasticity across the female lifespan. In this study, we aim to investigate the brain anatomical architecture of hormonal transition phases by directly comparing menarche, as a period of rising levels of steroid hormones, and menopause, as a time of declining levels. MethodsWe fit linear models on cross-sectional and linear mixed-effect models on longitudinal magnetic resonance imaging (MRI) datasets, to explore the effects of menarche onset (ABCD study data, Ncross-sectional=1274, Nlongitudinal=611) and transition into menopause (UK Biobank data, Ncross-sectional=1614, Nlongitudinal=212) on 66 cortical and 135 subcortical brain volumes, and to identify brain structures with opposing but regional overlapping effects in both periods. Models were adjusted for age and corrected for multiple comparison (P <.05; FDR-corrected). ResultsCross-sectionally, using a between-subject design, 83 brain volumes showed effects of menarche-onset and 17 volumes showed effects of menopause-transition. Of these, seven brain volumes were significantly affected by both transitional periods, showing opposing directional volume changes. Longitudinally, using a within-subject design, 56 brain volumes exhibited menarche effects, of which 46 replicated cross-sectionally. No menopause effect survived correction for multiple comparison, likely due to limited longitudinal sample size. ConclusionOur findings confirm regionally overlapping brain structural alteration between the two hormonal phases - menarche and menopause - showing the hypothesized opposite effect directions. Additionally, our results show the robustness of menarche effects, which converged across cross-sectional and longitudinal study designs. Taken together, our results contribute to a better understanding of hormone related neuroplasticity, emphasizing the importance of not only understanding individual phases, but understanding the overarching patterns across the female reproductive lifespan.

neuroscience↗

Inter- and intra-individual differences in brain sex map to neuroendocrine profiles

Sex hormone fluctuations modulate structural and functional brain dynamics, yet little is known how sex steroid levels map onto the expression of sex differences in the brain. Here, we trained machine learning models for brain sex classification based on anatomical structures in cross-sectional data of N = 1090 individuals (50% females, age matched). Applied to dense sampled data of one male and two females in different hormonal states (naturally cycling, oral contraceptive user, pregnancy), we linked inter- and intra-individual fluctuations in brain sex to neuroendocrine modulation. We found lower variation in brain sex across time in the male compared to the female subjects. Oral contraceptive use was associated with a more female-like brain, while (inverted) U-shaped brain sex trajectories emerged across menstrual cycle phases and pregnancy trimesters. Overall, our findings suggest that changes in brain sex capture hormone-related plasticity over time in dense sampled individuals.

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Higher glucose levels buffer against everyday stress load

Adaptive stress responses are dependent on the availability of energy and the bodys effectiveness in metabolizing glucose as fuel. However, it is not well understood if glucose levels contribute to the functional regulation of daily stress in healthy individuals. Here, we used 4,307 ratings of stress during a four-week period of ecological momentary assessment (EMA) with concurrent recordings from continuous glucose monitoring (CGM) in 91 participants (47 women). In accordance with the hypothesized metabolic link, we found that higher glucose levels were associated with lower self-reported stress (b = -.038, p = .035, controlling for mood). Crucially, dynamic changes in glucose levels also precipitated subsequent increases in stress levels (0-2h before EMA: p = .013; incremental effect 10-12h before: p < .001), with lower glucose levels associated with subsequent stress increases and elevated glucose with stress relief, highlighting the potential of monitoring physiological biosensor data to improve adaptive stress regulation. We conclude that metabolic signals, such as glucose, play an important role in channeling stress responsiveness in healthy adults, pointing to a pivotal avenue for improved interventions to avoid excessive stress experiences.

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Traces of parenthood but not pregnancy loss in UK Biobank structural brain MRI data

Pregnancy induces neuroanatomical changes in the human brain. Earlier studies detected traces of motherhood decades after childbirth. It is unclear whether these reflect persisting traces of pregnancy or effects of parenthood. We investigated effects of past birth and of pregnancy loss in women, and effects of fatherhood in men, using univariate and machine learning analyses on 205 regional brain volumes. A group of mothers and an age-matched sample of nulliparous women (N=4357 per group, mean age 63 years) from the UK Biobank, with no past pregnancy losses, showed significant volumetric group differences in 14 regions at Bonferroni-adjusted =.05. Likewise, we identified 18 significant group differences between age-matched samples of fathers and non-fathers of the same size (mean age 63.4), with 9 regions overlapping between sexes. Brain-wide association statistics for past live birth in mothers and those for fatherhood correlated (r = 0.55). XGBoost machine learning models trained to classify parenthood status separately in both datasets showed performance that was low, but significantly above chance (10-fold cross validation: AUC=0.56, p<1e-5 Motherhood classifier, AUC=0.54, p<1e-5, Fatherhood classifier, 10k permutations). We tested the motherhood classification model on an independent test sample comprising of four age-matched groups: 1. women who have never been pregnant, 2. women with past pregnancy loss but no live births, 3. women with live births but no pregnancy loss, and 4. women who experienced both. Class probability was significantly associated with live births, but not past loss. These findings may suggest that neuroanatomical patterns of past childbirth partly also reflect traces of parenthood and not solely persisting traces of past pregnancy, although a more detailed characterization of pregnancy loss data would be needed for full confirmation of this interpretation. Therefore, further research is needed to quantify the extent and understand the nature of these changes, particularly considering the known vulnerability for mental disorders associated with reproductive events.

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The elusive neural signature of emotion regulation capabilities: evidence from a large-scale consortium

Cognitive reappraisal is a fundamental emotion regulation strategy for mental and physical well-being, but how its neural mechanisms relate to individual differences remains poorly understood. In a consortium effort analyzing 40 fMRI datasets (N=2,175), we examined the relationship between neural activation during reappraisal tasks and three core individual difference indices of reappraisal capabilities: (1) trait questionnaires, (2) task-based affective ratings, and (3) amygdala down-regulation. Strikingly, there was no shared overlap across these three common indices. Only a very weak correlation emerged between amygdala down-regulation and task-based affective ratings. Whole-brain analyses revealed no reliable neural associations with trait questionnaires, and associations with task-based affective ratings fell outside canonical emotion regulation networks (e.g., prefrontal circuitry). Moreover, amygdala down-regulation, often interpreted as a stable individual marker, was confounded by person-specific whole-brain responses -- a limitation extending to fMRI research beyond the emotion regulation domain. These findings challenge the assumption that an individuals prefrontal activity is a valid indicator of their reappraisal capabilities and suggest that common trait, behavioral, and neural measures might capture distinct facets of emotion regulation. More broadly, our results highlight concrete methodological challenges for fMRI research on individual differences, with implications extending beyond emotion regulation to the neuroscience of personality, psychopathology, and general well-being.

neuroscience↗

Glucose levels are associated with mood, but the association is mediated by ratings of metabolic state

Hunger is commonly linked to negative mood and mood shifts are thought to arise from sensing the bodys internal state. However, it is unclear whether circulating glucose levels affect mood subconsciously or via subjectively sensed metabolic states. Here, we continuously monitored the interstitial glucose levels of 90 healthy adults for four weeks while they completed ecological momentary assessments (EMA; M=47 runs per participant) to rate their mood and metabolic states. As expected, hungry participants reported lower mood, and metabolic state ratings were associated with glucose levels. Although glucose levels were associated with mood, the metabolic state ratings fully mediated this association. Individual differences reflecting metabolic health (i.e., BMI and insulin resistance) did not affect the interaction between glucose and metabolic state ratings on mood. Notably, individuals with higher interoceptive accuracy had fewer fluctuations in mood ratings. We conclude that hunger-related mood shifts depend on conscious sensing of the bodys internal state instead of acting subconsciously. Our study highlights the relevance of considering the self-report of bodily signals in understanding mood shifts, offering new fundamental insights into mood regulation mechanisms. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIAlthough glucose is linked to satiety and hunger to negative mood, it is not known if this is due to the conscious perception of metabolic states. C_LI What this study addsO_LIThe longitudinal study design leveraging continuous glucose monitoring (CGM) and ecological momentary assessment (EMA) over four weeks, offers a unique perspective on glucose-mood interactions in naturalistic settings. C_LIO_LIWe found that the link between mood and glucose levels is fully mediated by consciously sensed metabolic states, clarifying the interoceptive link between glucose and mood. C_LI How this study might affect research, practice or policyO_LIMood is shaped by perceived metabolic states highlighting the relevance of metabolic health for mental health. C_LIO_LIThese insights improve our understanding of the association between metabolic and mental disorders. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/645871v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@7b1981org.highwire.dtl.DTLVardef@1c7a1f2org.highwire.dtl.DTLVardef@15944eaorg.highwire.dtl.DTLVardef@1bb802a_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Social stress, cortisol awakening response and sex: Impact on hippocampus and amygdala volume

ObjectiveVolumes of the hippocampus and amygdala, both major hubs for neural stress regulation amongst others, are influenced by social stressors, cortisol awakening response (CAR) and sex, i.e. psychological and physiological stress factors. Importantly, the interplay of these different factors in affecting the morphology of both brain regions remains unclear. This study aimed to elucidate the intricate influence of these factors on grey matter volumes (GMV) of the hippocampus and amygdala. MethodsWe analyzed associations between structural brain data, self-reported chronic social stress (including subscales on social tension, social overload, lack of social recognition and social isolation) and CAR of 83 healthy participants (40 females) with multiple regression analyses. ResultsIn males, but not females, higher social tension predicted lower bilateral hippocampus GMV. In individuals not showing the typical CAR, higher social tension predicted reduced bilateral hippocampus GMV. Amygdala GMV was also related to social stress and CAR, with social overload associated with reduced amygdala GMV in individuals not showing the typical CAR, while the opposite pattern emerged in those with an atypical CAR. ConclusionsChronic social stress is associated with hippocampus and amygdala volumes, interacting with CAR and sex. The brain morphology in males and in individuals with atypical CAR seems to be more vulnerable to chronic social stress. Our findings enhance our understanding of how brain architecture, social stress, CAR patterns and sex shape individual stress responses.

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To start or to discontinue the pill - changes in progestogens reflected by resting-state connectivity and positive mood

Oral contraceptive (OC) intake has been associated with alterations in functional brain architecture and socio-affective processes. However, most previous studies have been limited by cross-sectional designs and/or did not account for synthetic sex hormone concentrations. The aim of this longitudinal study was to determine the effects of starting vs discontinuing OCs on socio-affective functions such as mood and emotion cognition, and to identify their possible neuroendocrinological substrates. To this end, 88 young healthy women performed the behavioral and fMRI measures twice, three to eight months apart: 26 natural cycling women twice during menstruation, 26 OC users twice during OC intake, 25 OC discontinuers and 11 OC starters before and after discontinuation or start, respectively. In addition to mean-based analyses, we used intersubject representational similarity analyses to determine relationships between interindividual variability in within-subject changes of hormone profiles, including concentrations of endogenous and synthetic hormones, region-specific resting state functional connectivity (parcelwise RSFC) and socio-affective measures. Across the whole sample, interindividual patterns of changes in RSFC of fronto-parietal regions, parts of the left hippocampus and the right cerebellum reflected change patterns of progestogen levels. For the right superior orbitofrontal gyrus (OFG), a trinity of idiosyncratic patterns was found in changes of progestogens, RSFC and positive mood. Active OC intake was associated with higher self-reported depressive symptoms in OC discontinuers (and starters). Emotion recognition performance was not associated with changes in hormone profiles or RSFC. Overall, progestogens rather than estrogens appear to be associated with functional brain architecture of the frontal and subcortical/cerebellar regions and positive mood. The right superior OFG represents a possible neural substrate for progestogen-induced changes in positive mood. This study indicates the importance of a multidimensional, longitudinal approach when being interested in effects of hormonal contraception on womens brain and behavior.

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Accurate sex prediction of cisgender and transgender individuals without brain size bias

Brain size differs substantially between human males and females. This difference in total intracranial volume (TIV) can cause bias when employing machine-learning approaches for the investigation of sex differences in brain morphology. TIV-biased models will likely not capture actual qualitative sex differences in brain organization but rather learn to classify an individuals sex based on brain size differences, thus leading to spurious and misleading conclusions, for example when comparing brain morphology between cisgender- and transgender individuals. Here, TIV bias in sex classification models applied to cis- and transgender individuals was systematically investigated by controlling for brain size either through featurewise confound removal or by matching training samples for TIV. Our results provide evidence that non-TIV-biased models can classify the sex of both cis- and transgender individuals with high accuracy, highlighting the importance of appropriate modelling to avoid bias in automated decision making. TeaserAccurate non-biased structural sex classification in cis- and transgender individuals by matching training samples for TIV

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Interrelated effects of age and parenthood on whole-brain controllability: protective effects of parenthood in mothers

BackgroundControllability is a measure of the brains ability to orchestrate neural activity which can be quantified in terms of properties of the brains network connectivity. Evidence from the literature suggests that aging can exert a general effect on whole-brain controllability. Mounting evidence, on the other hand, suggests that parenthood and motherhood in particular lead to long-lasting changes in brain architecture that effectively slow down brain aging. We hypothesize that parenthood might preserve brain controllability properties from aging. MethodsIn a sample of 814 healthy individuals (aged 33.9{+/-}12.7 years, 522 females), we estimate whole-brain controllability and compare the aging effects in subjects with vs. those without children. We use diffusion tensor imaging (DTI) to estimate the brain structural connectome. The level of brain control is then calculated from the connectomic properties of the brain structure. Specifically, we measure the network control over many low-energy state transitions (average controllability) and the network control over difficult-to-reach states (modal controllability). Results and conclusionIn nulliparous females, whole-brain average controllability increases, and modal controllability decreases with age, a trend that we do not observe in parous females. Statistical comparison of the controllability metrics shows that modal controllability is higher and average controllability is lower in parous females compared to nulliparous females. In men, we observed the same trend, but the difference between nulliparous and parous males do not reach statistical significance. Our results provide strong evidence that parenthood contradicts aging effects on brain controllability and the effect is stronger in mothers.

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Connectivity patterns of task-specific brain networks allow individual prediction of cognitive symptom dimension of schizophrenia and link to molecular architecture

BackgroundDespite the marked inter-individual variability in the clinical presentation of schizophrenia, it remains unclear the extent to which individual dimensions of psychopathology may be reflected in variability across the collective set of functional brain connections. Here, we address this question using network-based predictive modeling of individual psychopathology along four data-driven symptom dimensions. Follow-up analyses assess the molecular underpinnings of predictive networks by relating them to neurotransmitter-receptor distribution patterns. MethodsWe investigated resting-state fMRI data from 147 schizophrenia patients recruited at seven sites. Individual expression along negative, positive, affective, and cognitive symptom dimensions was predicted using relevance vector machine based on functional connectivity within 17 meta-analytic task-networks following a repeated 10-fold cross-validation and leave-one-site-out analyses. Results were validated in an independent sample. Networks robustly predicting individual symptom dimensions were spatially correlated with density maps of nine receptors/transporters from prior molecular imaging in healthy populations. ResultsTen-fold and leave-one-site-out analyses revealed five predictive network-symptom associations. Connectivity within theory-of-mind, cognitive reappraisal, and mirror neuron networks predicted negative, positive, and affective symptom dimensions, respectively. Cognitive dimension was predicted by theory-of-mind and socio-affective-default networks. Importantly, these predictions generalized to the independent sample. Intriguingly, these two networks were positively associated with D1 dopamine receptor and serotonin reuptake transporter densities as well as dopamine-synthesis-capacity. ConclusionsWe revealed a robust association between intrinsic functional connectivity within networks for socio-affective processes and the cognitive dimension of psychopathology. By investigating the molecular architecture, the present work links dopaminergic and serotonergic systems with the functional topography of brain networks underlying cognitive symptoms in schizophrenia.

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Emotional responsiveness task in emotional distress: correlated of functional neuroimaging in anorexia and bulimia

AimThe present study aims to extend the knowledge of the neural correlates of emotion processing in first episode subjects affected by anorexia nervosa (AN) or bulimia nervosa (BN). We applied an emotional distress paradigm targeting negative emotions thought to be relevant for interpersonal difficulties and therapeutic resistance mechanisms. MethodsThe current study applied a neuroimaging paradigm eliciting affective responses to 44 female participants with newly diagnosed AN or BN and 20 matched controls. The measurements also included an extensive assessment comprised of clinical scales, neuropsychological tests, measures of emotion processing and empathy. ResultsAN and BN did not differ from controls in terms of emotional response, emotion matching, self-reported empathy and cognitive performance. However, scores of eating disorder and psychopathological clinical scores, as well alexithymia levels, were increased in AN and BN. On a neural level, no significant group differences emerged, even when focusing on a region of interest selected a priori: the amygdala. ConclusionsOur data are against the hypothesis that participants with AN or BN display a reduced emotional responsiveness. This supports the hypothesis that relational difficulties, as well as therapeutic resistance, are not secondary to simple difficulty in feeling and identifying basic negative emotions in AN and BN participants.

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Brain-based ranking of cognitive domains to predict schizophrenia

Schizophrenia is a devastating brain disorder that disturbs sensory perception, motor action, and abstract thought. Its clinical phenotype implies dysfunction of various mental domains, which has motivated a series of theories regarding the underlying pathophysiology. Aiming at a predictive benchmark of a catalogue of cognitive functions, we developed a bottom-up machine-learning strategy and provide a proof of principle in a multi-site clinical dataset (n=324). Existing neuroscientific knowledge on diverse cognitive domains was first condensed into neuro-topographical maps. We then examined how the ensuing meta-analytic cognitive priors can distinguish patients and controls using brain morphology and intrinsic functional connectivity. Some affected cognitive domains supported well-studied directions of research on auditory evaluation and social cognition. However, rarely suspected cognitive domains also emerged as disease-relevant, including self-oriented processing of bodily sensations in gustation and pain. Such algorithmic charting of the cognitive landscape can be used to make targeted recommendations for future mental health research.

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